Country：China

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: In addition to oncological and treatment factors, the outcomes of cancer treatment are greatly influenced by host factors, such as the nutritional status. The aim of this study was to evaluate the association between the preoperative nutritional status and the prognosis of colorectal cancer patients using three nutritional indices. PATIENTS AND METHODS: The target cohort consisted of 529 patients with stage I-III colorectal cancer, who underwent curative surgery between January 2015 and December 2019. The nutritional indices were calculated according to the equations that follow. Prognostic nutritional index (PNI)=10×serum albumin concentration (g/dl) +0.005×peripheral lymphocyte count (/μl). Nutritional risk index (NRI)=15.19×serum albumin concentration (g/dl)+41.7×present weight/usual weight. Geriatric nutritional risk index (GNRI)=14.89×serum albumin concentration (g/dl)+41.7×present weight/ideal weight. Ideal weight was calculated as follows: height(cm)-100-[(height(cm)-150)/4] for men and height(cm)-100-[(height(cm)-150)/2.5] for women. RESULTS: In common with all nutritional indices (PNI, NRI and GNRI), the low-nutritional index group had significantly lower relapse-free and overall survival rates than the high-nutritional index group. Furthermore, a subgroup analysis according to the NRI showed the association of the NRI with the patient prognosis for each stage. CONCLUSION: The preoperative nutritional status may have a close relationship with the prognosis in patients who receive curative surgery for colorectal cancer.

DOI： 10.21873/invivo.13265

PubMed

DOI： 10.34449/j0096.07.02_0032-0034

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Recently, the prognostic immune and nutritional index (PINI), which is calculated from the peripheral monocyte count and serum albumin level, has been reported to be useful as a prognostic marker in Korean and Chinese patients with colorectal cancer. The present study therefore examined the usefulness of the PINI as a marker for predicting the prognosis in Japanese colorectal cancer patients. PATIENTS AND METHODS: A total of 529 patients who underwent curative surgery for stage I-III colorectal cancer between January 2015 and December 2019 were enrolled in this study. The PINI was calculated as [serum albumin concentration (g/dl)×0.9]-[peripheral monocyte count (mm3)×0.0007]. RESULTS: The median PINI was 3.242 (range=1.250-4.091). A receiver operating characteristic curve analysis revealed that the appropriate cut-off value of the PINI was 3.047. The low-PINI group had significantly lower relapse-free and overall survival rates than the high-PINI group (p<0.0001, p<0.0001, respectively). CONCLUSION: The PINI based on host factors is useful as a prognostic marker for Japanese patients with stage I-III colorectal cancer.

DOI： 10.21873/cdp.10223

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). CONCLUSION: In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

DOI： 10.1186/s12885-023-10631-w

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Hypoxia is significantly associated with the development of drug resistance, and endocrine therapy is ineffective against hormone receptor (HR)-positive breast cancer in hypoxic tumor environments. Eribulin has a unique anticancer effect in breast cancer cells and improves tumor hypoxia by vascular remodeling. Therefore, we investigated the effect of eribulin on HR-positive breast cancer cells that were resistant to endocrine blockade. MATERIALS AND METHODS: We established hypoxia-resistant breast cancer cell lines by continuous culture in a hypoxic environment. Parental and hypoxia-resistant cell lines were treated with eribulin and/or tamoxifen, and estrogen receptor (ER)-, epithelial-mesenchymal transition-, and hypoxia-related gene and protein expression changes in each surviving cell line were assessed. In addition, proliferation was assessed after eribulin treatment in the parental and hypoxia-resistant cell lines. We also assessed the effect of eribulin in vivo using subcutaneous xenograft models. RESULTS: Hypoxia-resistant cell lines showed significantly decreased expression of epithelial and ER-related markers and exhibited a higher level of resistance to tamoxifen. Conversely, eribulin treatment increased epithelial and ER-related gene and protein expression in hypoxia-resistant cell lines and enhanced the anticancer effect of tamoxifen. In in vivo xenograft models, eribulin treatment of hypoxia- and tamoxifen-resistant tumors slightly induced the re-expression of ER. In addition, hypoxia-resistant tumors treated with eribulin tended to respond better to tamoxifen. CONCLUSION: Eribulin ameliorated the aggressive behavior caused by hypoxia and induced the re-expression of ER in hypoxia-resistant breast cancer cells. Eribulin treatment of HR-positive breast cancer may resensitize cells to hormone blockade.

DOI： 10.21873/anticanres.16196

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Smoking has been a proven carcinogenic risk factor for various cancers, including breast cancer. Furthermore, smoking has been recognized as a prognostic factor of breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) used in combination with chemotherapy to treat breast cancer. We, herein, investigated the effect of smoking on the prognosis of unresectable breast cancer patients who received bevacizumab plus weekly paclitaxel. PATIENTS AND METHODS: From April 2011 to June 2022, 131 patients received bevacizumab plus weekly paclitaxel for unresectable breast cancer. At their first visit to our hospital, smoking status (i.e., period of smoking and amount of smoking per day) was evaluated by interview, and packs-years were calculated. RESULTS: Time to treatment failure (TTF) was significantly longer in the high packs-years group than the low packs-years group (p=0.010, log-rank). The log-rank test showed that the high packs-years group had a significantly longer overall survival than the low packs-years group (p=0.049, log-rank). Multivariate analysis of TTF revealed that progesterone receptor (p=0.005, HR=0.408) and packs-years (p=0.007, HR=0.391) were independent factors. CONCLUSION: A history of smoking may impact prognosis of combination chemotherapy with bevacizumab for advanced breast cancer treatment.

DOI： 10.21873/anticanres.16227

PubMed

乳癌手術における広範囲の皮膚欠損部を閉鎖する手技の一つとして,横転皮弁の応用型であるrhomboid flap法を当科では採用しており,その治療成績について報告する。対象は2020年7月～2021年3月にかけてrhomboid flap法を併用して原発巣切除を施行した乳癌症例5例であり,短期成績および長期成績について検証した。創感染2例,皮弁虚血で2例を認め,術後在院日数中央値は9日と,単純縫縮可能症例と比較して長期間に及ぶ傾向にあった。また,観察期間中に再発を認めたのは1例のみであり,無増悪生存期間中央値は332日であった。rhomboid flap法の術後合併症は様々な工夫により制御可能であり,簡便かつ短時間に広範囲の皮膚欠損を修復できる手技の一つとして有用であると考えられた。(著者抄録)

がん遺伝子パネル検査が治療方針の決定に寄与した1例を経験したので報告する.59歳,女性.左乳房の湿疹を自覚し前医を受診,皮膚浸潤を伴う左乳癌が疑われ紹介となった.精査にて右乳腺にも乳癌が認められ,両側乳癌と診断された.右側が浸潤性乳管癌cT1N1M0 stageIIA(Luminal HER),左側が浸潤性乳管癌 cT4N3M0 stageIIIC(Luminal)であった.ここで化学療法(ドセタキセル+ペルツズマブ+トラスツズマブ)を施行したところ,腫瘍縮小を認めたために手術に至った.術後1年,頸椎および胸椎に骨転移再発を認めたために治療を変更,その後6ヵ月目に肝転移が認められた.そこで,肝生検を行いサブタイプの再確認のうえで,再度治療を変更した.治療効果を認めたが,有害事象のため約6ヵ月で継続困難となった.ここで,がん遺伝子パネル検査(FoundationOne)を行ったところ,BRCA2遺伝子の生殖細胞変異が確認された.本検査については,新たな治療の可能性につながるために積極的に実施するのが望ましいと考えられた.(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Lipid metabolism has been recently reported to affect the prognosis and tumor immune activity in cancer patients. However, the effect of lipid metabolism on chemosensitivity in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear. METHODS: We examined 327 patients with breast cancer who were treated with NAC followed by curative surgery. The correlations between the serum levels of total cholesterol (TC) and triglyceride (TG) and the clinicopathological features, including the efficacy of NAC, neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC), were evaluated retrospectively. RESULTS: Serum TG levels were increased after NAC in all the subtypes, and the rate of change was the highest, especially in triple-negative breast cancer (TNBC) (21.0% → 48.1%). In addition, only TNBC patients with an objective response (OR) had significantly higher TG levels after NAC than those without (P = 0.049). Patients with a high ALC before NAC had significantly higher TG levels after NAC than patients with all breast cancer (P = 0.001), HER2-enriched breast cancer (P = 0.021), and TNBC (P = 0.008). Patients with a low NLR before NAC had significantly higher TG levels after NAC only among patients with TNBC (P = 0.025). In patients with human epidermal growth factor receptor 2-enriched breast cancer, the group with normal TC levels before NAC had significantly better OS than those with high TC levels (P = 0.013, log-rank test), and in patients with TNBC, the group with high TC levels after NAC had significantly better OS than those with normal TC levels (P = 0.014, log-rank test). CONCLUSIONS: Good systemic immune activity and chemosensitivity may be associated with lipid metabolism regulated by NAC in TNBC patients.

DOI： 10.1186/s40001-022-00964-w

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Intraoperative blood loss (IBL) during the surgical treatment of various cancers affects complication rates and prognosis. However, few studies have examined the importance of minimal IBL in breast cancer surgery. We used factor analysis to examine the prognostic importance of IBL in breast cancer. PATIENTS AND METHODS: One hundred ninety-seven patients who underwent mastectomy plus axillary lymph node dissection (level II) after preoperative chemotherapy between June 2007 and June 2021 were included. Pearson's Chi-square test was used to confirm the relationships between different factors. Kaplan-Meier survival curves and the log-rank test were used to examine prognosis. Logistic regression was performed using a Cox proportional hazards model. RESULTS: The median IBL was 55.0 g (range=5.0-420.0 g). IBL was <100 g in 143 patients (72.5%), 100-200 g in 39 patients (19.8%), and >200 g in 15 patients (7.6%). Logistic regression analysis showed that patients with IBL ≥200 g had a significantly worse prognosis (disease-free survival: p=0.003, log-rank test; overall survival: p<0.001, log-rank test). Factor analysis revealed that HER2-negative status (p=0.015), non-pathological complete response (p=0.031), obesity (p=0.001), heavy smoking (p=0.047), and diabetes mellitus (p=0.004) were significantly associated with increased IBL. CONCLUSION: IBL in breast cancer was correlated with various clinicopathological factors associated with a poor prognosis, suggesting that increased IBL may be associated with poor prognosis in breast cancer as well.

DOI： 10.21873/anticanres.16149

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy. In this study, we evaluated the predictors for FN according to neoadjuvant chemotherapy (NAC) in all breast cancer subtypes. PATIENTS AND METHODS: We examined 327 patients with breast cancer treated with NAC. The correlation between the development of FN and clinicopathological features, including systemic inflammatory markers, and prognosis was evaluated retrospectively. RESULTS: There were no significant differences between patients with and without FN in terms of disease-free survival or overall survival (p=0.562, p=0.149, log-rank, respectively). Low body mass index (BMI) (p<0.001), white blood cells (WBC) at baseline (p=0.008), and NAC regimen (p=0.026) significantly related with FN in all patients with breast cancer. Moreover, among patients with hormone receptor-positive/human epidermal growth factor receptor 2-positive breast cancer, low WBC (p=0.007) and low absolute lymphocyte counts (ALC) at baseline (p=0.039) were significantly associated with FN, and overall survival was significantly worse in patients with FN development (p=0.039, log-rank). CONCLUSION: Poor immune activity-related factors, low ALC or BMI, may be useful to predict the development of FN in patients with breast cancer.

DOI： 10.21873/anticanres.16156

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: As D-dimer levels have been reported to reflect cancer activity, preoperative D-dimer levels may serve as a prognostic marker in patients with colorectal cancer. The aim of this study was to evaluate the prognostic significance of preoperative D-dimer levels in patients with stage I-III colorectal cancer who underwent curative surgery. PATIENTS AND METHODS: A total of 264 patients who underwent curative surgery for stage I-III colorectal cancer between January 2015 and December 2019 were enrolled in this study. RESULTS: The median preoperative D-dimer level was 0.8 μg/ml (range=0.4-42.5 μg/ml). Based on the results of a receiver operating characteristic curve analysis, we set 1.45 as the cut-off value and classified patients into the low (n=215) and high D-dimer (n=49) groups. The high D-dimer group had significantly lower relapse-free and overall survival in comparison to the low D-dimer group (p<0.0001, p<0.0001, respectively). CONCLUSION: Preoperative D-dimer levels can serve as a prognostic marker for stage I-III colorectal cancer.

DOI： 10.21873/cdp.10177

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Predictive markers for survival and therapeutic efficacy in stage IV colorectal cancer have not been established. As described in our previous report, D-dimer levels may have potential utility as an indicator of cancer activity. The present study evaluated the significance of the D-dimer level as a marker for the survival and treatment outcomes in patients with stage IV colorectal cancer. PATIENTS AND METHODS: A total of 34 patients who underwent surgery for stage IV colorectal cancer between February 2017 and October 2019 were enrolled. The D-dimer level was measured using a blood sample obtained at the first visit to our hospital. RESULTS: The median preoperative D-dimer level was 1.2 μg/ml (range=0.5-41.0 μg/ml). We divided patients into two groups using a D-dimer level of 2.0 μg/ml as the cut-off value based on receiver operating characteristic curve analysis. The group with a high-D-dimer-level had a significantly shorter overall survival than that with a low D-dimer level. Progression-free survival after first-line chemotherapy tended to be better in those with a low D-dimer level group than in the high-D-dimer-level group. CONCLUSION: The preoperative D-dimer level may be a useful indicator for survival and chemotherapeutic outcome in patients with stage IV colorectal cancer.

DOI： 10.21873/invivo.13097

PubMed

<p>Here, we report a case in which cancer multi-gene panel testing contributed to treatment. The patient was a 59-year-old woman. She was referred to our hospital for suspected left breast cancer with skin invasion. The right breast presented with invasive ductal carcinoma cT1N1M0 stage IIA (Luminal HER) and the left one with invasive ductal carcinoma cT4N3M0 stage IIIC (Luminal). The patient was treated with combination chemotherapy (docetaxel+pertuzumab+trastuzumab), and surgery was performed after tumor shrinkage was observed. Postoperatively, the patient was administered with adjuvant chemotherapy and endocrine therapy according to the subtype. One year postoperatively, treatment was switched due to the recurrence of bone metastases in the cervical and thoracic spine, followed by liver metastasis after 6 months. Liver biopsy was performed to reconfirm the subtype, and treatment was switched again. The patient was treated successfully, although adverse events rendered the continuation of treatment difficult after approximately 6 months. Therefore, cancer multi-gene panel testing (FoundationOne^®) was performed, and a germline mutation in the <i>BRCA2</i> gene was confirmed. We strongly recommend the inclusion of multi-gene panel testing in cancer management, as it may offer new treatment opportunities.</p>

DOI： 10.3919/jjsa.84.265

DOI： 10.1021/acsptsci.2c00121

PubMed

パルボシクリブ(PAL)125mg/dまたはアベマシクリブ(ABE)300mg/dを投与された進行乳癌患者を対象に、後方視的に検討した。薬剤の減量または中止を要する副作用を重大な有害事象(SAE)と定義した。PAL投与患者の36%(9/25)およびABE投与患者の27.3%(9/33)にSAEが出現した。PAL群およびABE群のSAE出現例ではそれぞれ、投与前の白血球(WBC)数および血清アルブミン(ALB)値が非出現例と比べて有意に低かった。ROC曲線解析の結果、WBC数およびALB値の至適カットオフ値はそれぞれ、5700/μLおよび4.0g/dLであった。ALB値>4g/dLの患者においてABEによるSAEの出現率はPALによるSAEの出現率より低かった。以上の結果から、投与前WBC数≦5700μLおよびALB値≦4.0g/dLはそれぞれ、PALおよびABEによるSAEの危険因子であり、ALB高値はABEを選択する指標になると考えられた。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Smoking worsens breast cancer prognosis. It has been reported that tobacco components directly reach the mammary gland tissue, causing smoking-related DNA damage and biological effects. We hypothesized that smoking may have characteristics that affect the therapeutic effect and clinical course in patients with stage IV hormone receptor-positive breast cancer (HRBC) who received endocrine therapy as the first-line treatment. PATIENTS AND METHODS: Fifty-six patients diagnosed with stage IV HRBC were treated with endocrine therapy as the first-line treatment. Before treatment, the period and amount of smoking were confirmed through patient interviews, and each pack-year was recorded. RESULTS: Disease progression with new metastases was more frequent in smokers than non-smokers during endocrine therapy as first-line treatment (p=0.034). Furthermore, as the pack-year increased, new metastases tended to appear [pack-year ≤15; hazard ratio (HR)=1.929, p=0.507; pack-year 15-30, HR=3.857, p=0.223; pack-year >30, HR=7.714, p=0.028]. CONCLUSION: In stage IV HRBC, smoking increases the metastatic potential of breast cancer, suggesting that changes in its biology may lead to poor prognosis.

DOI： 10.21873/anticanres.15888

PubMed

DOI： 10.1002/advs.202201416

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Tumor microenvironment (TME) assessment is considered to play an important role in the prediction of prognosis and therapeutic response following breast cancer treatment. No consensus has been reached regarding evaluation methods despite reports on the utilization of tumor-infiltrating lymphocytes (TILs) for immune TME (iTME) monitoring. Optimum timing of iTME assessment has not yet been established. PATIENTS AND METHODS: Two hundred thirty-nine patients were treated with neoadjuvant chemotherapy (NAC). During the period from diagnostic needle biopsy to NAC initiation for breast cancer, the optimal evaluation timing was examined using a receiver operating characteristic (ROC) curve analysis. RESULTS: A significant correlation between TILs and pathological complete response (pCR) was only observed in the short-term group (≤35 days) (p=0.033). Prognostic analysis revealed that in the short-term group, patients with high TIL levels had a significantly better survival prognosis relative to those with low TIL levels (>35 days) [disease-free survival (DFS): p=0.001, overall survival (OS): p=0.021]. TILs were identified as an independent factor affecting DFS in a multivariate analysis (p=0.008, hazard ratio=0.130). CONCLUSION: TIL assessment during NAC for breast cancer is a prognostic predictor only when performed at ≤35 days before NAC initiation.

DOI： 10.21873/cdp.10127

PubMed

DOI： 10.1002/anie.202117330

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Augmented reality (AR) is a new technology that provides new awareness by using a computer to extend the real environment perceived by humans. Optical see-through head-mounted displays (OST-HMD) are worn on the head and can faithfully generate an AR image by wearing the device on the head as a spectacle-type device. We developed an ultrasound-guided needle biopsy technique using OST-HMD for breast tumors. PATIENTS AND METHODS: Moverio BT-35E (Seiko Epson Corp, Nagano, Japan) was used as the OST-HMD device. This technique involves performing needle biopsy under direct vision via the gap at the bottom of the display while the ultrasound images are projected on the display of the OST-HMD worn on the head. RESULTS: With this technique, needle biopsy can be executed smoothly with no posture restrictions. A flip shade affixed to the OST-HMD has 2% transmittance, which enables clearer projection of the images. CONCLUSION: This article outlines the ultrasound-guided needle biopsy using OST-HMD. We established a safe and accurate biopsy technique with technological innovations using AR.

DOI： 10.21873/invivo.12772

PubMed

International / domestic magazine：International journal  

Although the incidence of hematological toxicity due to Trifluridine/tipiracil (FTD/TPI) treatment is high, the incidence of severe adverse events has been reported to be relatively low. However, it should be noted that patients with renal impairment are prone to severe hematological adverse events.

DOI： 10.1002/ccr3.5544

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs), which are indicators of immune response monitoring, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focused on TILs that exist within the FF and performed pathological evaluations. PATIENTS AND METHODS: Of the 320 patients treated with neoadjuvant chemotherapy (NAC), 239 subjects who were able to evaluate FF-TILs were targeted. Lymphocytes that infiltrate the FF are FF-TILs. RESULTS: The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p<0.001) and for all subtypes of triple-negative breast cancer (TNBC) (p=0.001), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p=0.010), and hormone receptor-positive breast cancer (HRBC) (p=0.003). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases [p<0.001, hazard ratio (HR)=0.198] and all subtypes of TNBC (p=0.006, HR=0.172), HER2BC (p=0.025, HR=0.135), and HRBC (p=0.007, HR=0.228). CONCLUSION: FF-TILs are possibly a useful factor for predicting recurrence of breast cancer after NAC.

DOI： 10.21873/anticanres.15612

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Lymphocytes that surround cancer participate in tumor-related immune responses and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs index the tumor microenvironment and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TIL density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of preoperative chemotherapy (POC) in BC patients who were aged either less than 45 years or more than 60 years. METHODS: We retrospectively examined the data of 356 breast cancer patients who underwent POC, including 75 patients aged ≤ 45 years and 116 patients aged > 60 years. Using pre-treatment needle biopsy specimens, TIL density was compared for each age group by Student's t-test. After analyzing different factors that affect TIL density, prognostic factors were also examined. RESULTS: Older patients with triple-negative BC had significantly lower TIL density than younger patients, while in human epidermal growth factor receptor 2 (HER2)-enriched BC, TIL density was significantly higher in the younger age group than that in the older age group. In addition, younger patients with HER2-rich breast cancer showed significantly higher complete pathological response rates than older patients with HER2-rich BC. In addition, significant differences in overall survival were observed among these patients with triple-negative BC. CONCLUSIONS: Our study suggests that younger BC patients possess significantly higher TIL density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

DOI： 10.1186/s12957-022-02513-5

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Therapeutic agents for dyslipidaemia, in particular statins, have been recently reported to suppress growth and metastasis of breast cancer. However, the predictive value of lipid control in breast cancer patients has not been discussed sufficiently. In addition, though immunometabolism is a relatively novel approach for tumour immunotherapy, the relationship between lipid metabolism and immune status has not been well documented. We therefore investigated the effects of lipid metabolism on antitumour immune response and cancer prognosis. METHODS: Except for patients with ductal carcinoma in situ, 938 patients treated with curative surgery were examined. The correlation between treatment for dyslipidaemia or serum lipid levels and clinicopathological features, including the prognosis, was evaluated retrospectively. Also, we stratified these results by intrinsic subtype of breast cancer, menopause, and type of therapeutic agents for dyslipidaemia. Moreover, neutrophil- to-lymphocyte ratio (NLR) and tumour-infiltrating lymphocytes (TILs) were used as indicators of systemic and local immune status, respectively. RESULTS: Of 194 patients treated for dyslipidaemia, recurrence-free survival (RFS) and overall survival (OS) did not differ significantly between users of drugs for dyslipidaemia and non-users (p = 0.775 and p = 0.304, log-rank, respectively). Among postmenopausal, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients treated for dyslipidaemia, the good serum lipid control group had significantly better RFS (p = 0.014, log-rank), lower postoperative NLR (p = 0.012), and higher TILs in resected tissues (p = 0.024) than the poor control group. Multivariate analysis showed that postoperative serum lipid levels were a risk factor for recurrence (hazard ratio = 4.722, 95% confidence interval 1.006-22.161, p = 0.049). CONCLUSIONS: Good control of serum lipid metabolism may improve the tumour immune microenvironment and prognosis in postmenopausal HR-positive/HER2-negative breast cancer patients.

DOI： 10.1186/s12885-022-09234-8

PubMed

症例は38歳,女性.乳児期にPrader-Willi症候群(PWS)と診断されていた.スクリーニング検査にて甲状腺右葉に結節性病変を指摘され,精査加療目的に当科を紹介受診.甲状腺癌が強く疑われたため,手術加療の方針となった.精神発達遅延のため興奮状態となることがあり,全身麻酔導入に難渋した.手術は甲状腺右葉+峡部を摘出し,術中迅速診断にて甲状腺乳頭癌の診断であったため,頸部リンパ節郭清を追加した.術前CTではリンパ節腫大は認めなかったが,病理学的には9個の転移リンパ節を認めた.術後2年9ヵ月経過した現在,明らかな再発は認めていない.PWS患者における悪性新生物の報告は極めて少なく,本症例は甲状腺乳頭癌の本邦で初めての報告となる.(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Eribulin, a non-taxane microtubule inhibitor, improves the tumor immune microenvironment via vascular remodeling. Systemic peripheral immune markers such as absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) have been reported as prognostic factors of patients treated with eribulin. However, the usefulness of the longitudinal changes of these blood parameters during eribulin treatment remains unknown. PATIENTS AND METHODS: A total of 97 patients with locally advanced or metastatic breast cancer treated with eribulin were recruited. ALC and NLR values were collected at each cycle of treatment. The correlation between ALC and NLR and prognosis and antitumor effects was retrospectively evaluated. RESULTS: Progression-free and overall survival for patients with a base line ALC ≥1,500/μl was significantly better than that for those with a lower ALC (p=0.049 and p=0.004, respectively). The mean ALC in the non-progressive disease (PD) group increased, while that in the PD group slightly decreased over time. A low ALC at the last cycle was significantly correlated with PD (p=0.030). Of the 64 patients with PD, 47 were classified as having progression due to a pre-existing lesion (PPL), and 17 patients were classified as having progression due to new metastasis (PNM). The mean ALC for the PPL group slightly increased during eribulin treatment, while that for the PNM group decreased. CONCLUSION: Eribulin treatment may have improved the immune status in eribulin responders. Monitoring ALC values may be useful for early assessment of response to therapy.

DOI： 10.21873/anticanres.15553

PubMed

DOI： 10.1002/adma.202106500

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3 and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC). PATIENTS AND METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry. RESULTS: The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p=0.038) and HER2-enriched breast cancer (HER2BC) (p=0.021), while the total number of pathological complete response (pCR) patients was greater (p<0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p<0.001 and p=0.02, respectively). Moreover, on multivariate analysis low-LAG-3 expression status was an independent predictor of favorable prognosis (TNBC: p=0.014, HR=8.124; HER2BC: p=0.048, HR=10.400). CONCLUSION: Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.

DOI： 10.21873/anticanres.15466

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

The patient was a 64-year-old woman. The patient was operated for left breast cancer(pT2N0M0, stage ⅡA, Luminal A). Eight years after surgery, CT findings revealed lung metastasis in the S8 and S9 areas of the left lung. The patient was treated with a combination of abemaciclib and letrozole, which resulted in a partial response(PR). One year after treatment, the lung metastases remained small, but multiple interstitial shadows appeared in both lower lung fields. The patient was diagnosed with drug-induced interstitial lung disease(Grade 1), and abemaciclib withdrawal and steroid therapy were initiated. After 3 months of treatment with prednisolone at 30 mg/day, the interstitial shadows tended to improve on CT, but a liver abscess was found in the S8 area of the right lobe of the liver. Prednisolone was tapered and abemaciclib was resumed at a dose of 200 mg/day, resulting in scarring of the lung injury and resolution of the liver abscess. The patient's PR was maintained for 18 months after relapse. We report a case of liver abscess during treatment of abemaciclib-induced interstitial lung disease.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy. PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327). CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.

DOI： 10.21873/anticanres.15487

PubMed

アベマシクリブの重大な有害事象として薬剤性肺障害がある。症例は64歳、女性。左乳癌にて手術を施行し、pT2N0M0、stage IIA、Luminal Aであった。術後8年、CTにて左肺S8、S9区域に約1cm大の肺転移が出現した。アベマシクリブおよびレトロゾールの併用療法を行い、治療効果は部分奏効(PR)が得られた。投与後1年、肺転移巣は縮小維持も両下肺野に多発する間質影の出現が確認された。薬剤性肺障害(Grade 1)と診断し、アベマシクリブ休薬およびステロイド治療を開始した。プレドニゾロン30mg/日の投与で発症後3ヵ月のCTにて間質影は改善傾向であったが、肝右葉S8区域に肝膿瘍が認められた。プレドニゾロンの漸減を進めるとともに、アベマシクリブを200mg/日に減量して再開したところ肺障害は瘢痕化、また肝膿瘍は消失した。再発後18ヵ月、PRを維持し治療継続している。今回われわれは、アベマシクリブ起因性肺障害治療中に肝膿瘍を併発した1例を経験したので報告する。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Objectives

The objective of this study was to develop and validate a state-of-the-art, deep learning (DL)-based model for detecting breast cancers on mammography.

Methods

Mammograms in a hospital development dataset, a hospital test dataset, and a clinic test dataset were retrospectively collected from January 2006 through December 2017 in Osaka City University Hospital and Medcity21 Clinic. The hospital development dataset and a publicly available digital database for screening mammography (DDSM) dataset were used to train and to validate the RetinaNet, one type of DL-based model, with five-fold cross-validation. The model’s sensitivity and mean false positive indications per image (mFPI) and partial area under the curve (AUC) with 1.0 mFPI for both test datasets were externally assessed with the test datasets.

Results

The hospital development dataset, hospital test dataset, clinic test dataset, and DDSM development dataset included a total of 3179 images (1448 malignant images), 491 images (225 malignant images), 2821 images (37 malignant images), and 1457 malignant images, respectively. The proposed model detected all cancers with a 0.45–0.47 mFPI and had partial AUCs of 0.93 in both test datasets.

Conclusions

The DL-based model developed for this study was able to detect all breast cancers with a very low mFPI. Our DL-based model achieved the highest performance to date, which might lead to improved diagnosis for breast cancer.

DOI： 10.1371/journal.pone.0265751

PubMed

<p>The patient was a 38-year-old woman who had been diagnosed with Prader-Willi syndrome (PWS) in infancy. A screening ultrasonography showed a nodular lesion in the right lobe of the thyroid gland, and the patient was referred to our department for further examination and treatment. As a result of a thorough examination, its lesion was strongly suspected to be malignant, and we decided to perform surgery. Because of a delay in mental development, the patient sometimes became agitated, and it was difficult to induce general anesthesia. The patient underwent surgery to remove the right lobe and isthmus of the thyroid gland, followed by additional cervical lymph node dissection due to the diagnosis of papillary thyroid cancer by intraoperative diagnosis. Preoperative CT scan showed no enlarged cervical lymph nodes, but nine microscopic metastatic lymph nodes were found. As of two years and nine months after the surgery, no apparent recurrence has been observed. There are very few reports of malignant neoplasms in PWS patients, and this is the first report of papillary thyroid carcinoma with PWS in Japan.</p>

DOI： 10.3919/jjsa.83.281

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: <i>p</i> = 0.007; abemaciclib: <i>p</i> = 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) <i>vs.</i> 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07–583, <i>p</i> = 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.</p>

DOI： 10.1248/bpb.b22-00338

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

For qualitative diagnosis of breast mass, core needle biopsy(CNB)and fine-needle aspiration biopsy cytology(FNAC)are widely used. Overseas, vacuum-assisted biopsy(VAB)is often the first choice for qualitative diagnosis, and its proper use has become a clinical issue. In addition, with the progress of diagnostic imaging in recent years, the chances of finding micro-lesions such as ductal carcinoma in situ(DCIS)are increasing. Since a sufficient amount of tissue sample is required for these diagnoses and abundant biopsy materials are required, tissue biopsy by VAB may be desirable. The advantage of tissue biopsy with VAB is that accurate definitive diagnosis is possible by collecting a sufficient amount of tissue to obtain pretreatment tissue information. On the other hand, there is concern that patient stress may occur, such as hematoma formation after puncture and invasion by a thick puncture needle. It is lightweight and has an ergonomic design that provides stable grip. New technological innovations in this device may contribute to the reduction of patient stress, and are expected to be used in the future. We outline the experience of using BD EleVationTM in breast suction tissue biopsy at our institution.

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 78-year-old woman with a left breast cancer was examined at our institute. Ultrasonography showed 48 mm sized mass at zone C of the left breast, and left axillary lymph node swelling. Pathological examination of core needle biopsy revealed invasive ductal carcinoma and lymph node metastasis. In addition, contrast computed tomography showed 30 mm sized an hypovascular mass at pancreatic body involved the portal vein. Endoscopic ultrasound guided fine needle aspiration biopsy of the pancreas revealed adenocarcinoma. The diagnosis was synchronous double cancer including borderline resectable pancreatic body cancer and left breast cancer, and she received neoadjuvant chemotherapy consisting of gemcitabine and nab-paclitaxel. The effect of neoadjuvant chemotherapy was judged to be stable disease for breast cancer, partial response for pancreatic cancer. Then, she underwent pancreatosplenectomy with portal vein and gastroduodenal artery resection and reconstruction, left mastectomy and axillary lymph node dissection. Pathologic examination of the excised specimen revealed the diagnosis of breast cancer with osseous/cartilaginous differentiation and pancreatic moderately differentiated adenocarcinoma. She was treated with fluorouracil, epirubicin, and cyclophosphamide as adjuvant therapy, and there has been no recurrence.

PubMed

症例は78歳、女性。左乳房腫瘤を主訴に当院を受診した。超音波検査で左乳腺C区域に48mmの乳腺腫瘤と腋窩リンパ節腫大を指摘され、針生検で浸潤性乳管癌とリンパ節転移の診断であった。造影CT検査で門脈浸潤を伴う30mmの膵体部腫瘤が指摘され、EUS-FNAで腺癌を認めた。左乳癌および切除可能境界膵体部癌の同時性重複癌と診断し、術前化学療法としてgemcitabine+nab-paclitaxel療法を施行した。効果判定は乳癌がSD、膵癌がPRで治癒切除可能と判断し、脾合併膵体尾部切除術、門脈・胃十二指腸動脈合併切除再建術、左乳房全摘術および左腋窩リンパ節郭清術を行った。病理組織検査で骨・軟骨化生を伴う乳癌および膵中分化型腺癌の診断であった。術後補助療法としてfluorouracil+epirubicin+cyclophosphamide療法を施行、現在無再発で経過している。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status of patients and to be correlated with their prognosis and therapeutic outcomes. However, the characteristics of the local immune status in metastatic tumors is poorly understood, as primary tumors have been the focus in most previous studies. In addition, the local immune status may be influenced by preoperative chemotherapy. The present study aimed therefore to investigate the relationship between the degree of TIL infiltration and the prognosis in patients with curative resection of colorectal cancer liver metastases and to examine the effects of preoperative chemotherapy on the function of immune cells. A total of 108 patients who underwent curative resection of colorectal cancer liver metastases in our department between May 1996 and January 2017 were enrolled in the present study. Peripheral blood samples were obtained within two weeks before surgery. TIL infiltration was evaluated by immunohistochemical staining of surgically resected specimens of liver metastases using anti-CD8/CD3 antibodies. The mean number of TILs in five different fields was calculated, and patients were classified into a high-TIL group and a low-TIL group. Furthermore, patients were divided into three groups as follows: i) A group of patients who did not receive preoperative chemotherapy; ii) a group of patients who received short-term preoperative chemotherapy for <6 months; and iii) a group of patients who received long-term preoperative chemotherapy for ≥6 months. The results demonstrated that the density of TILs in colorectal liver metastases was not correlated with the absolute peripheral lymphocyte count in all patients. Furthermore, the degree of CD8+TIL infiltration in liver metastases was significantly lower in the recurrence group compared with the recurrence-free group following hepatectomy. In all patients with colorectal liver metastases, the degree of CD8+TIL infiltration was significantly associated with the relapse-free and overall survival. In patients without preoperative chemotherapy, the degree of CD8+TIL infiltration was significantly associated with the relapse-free survival, and a high CD8+TIL presence tended to have a better effect on the overall survival than a low CD8+TIL presence. In the short-term chemotherapy group, the degree of CD8+TIL infiltration was significantly associated with the relapse-free and overall survival. In the long-term chemotherapy group, there were no significant differences between the high- and low- CD8+TIL groups in the relapse-free and overall survival. In contrast to CD8+TILs, CD3+TILs showed a poor prognostic ability. In summary, the degree of CD8+TIL infiltration in colorectal cancer liver metastases may be correlated with patient prognosis. However, in patients who received long-term chemotherapy before surgery, the degree of TIL infiltration was not necessarily associated with prognosis as the anti-tumor effects of TILs may decrease. The degree of CD8+TIL infiltration may therefore be considered as a useful prognostic factor in patients with colorectal liver metastases, but the prognostic accuracy may decrease in patients who received long-term chemotherapy.

DOI： 10.3892/ol.2021.13098

PubMed

乳腺腫瘤に対する質的診断では針生検(CNB)や穿刺吸引細胞診(FNAC)などが広く行われている。海外では吸引式乳腺組織生検(VAB)を質的診断の第一選択とする場合も多く、その使い分けは臨床的課題となっている。VABによる組織生検の利点は、治療前の組織情報を獲得するために十分な組織量を採取することで、正確な確定診断が可能となることである。一方で、穿刺後の血腫形成や太い穿刺針による侵襲など、患者ストレスが生じることも懸念される。昨今、本邦においてもVABにおける新たなデバイスとして、BD EleVationが使用可能となり注目されている。このデバイスは単回穿刺での複数の検体採取や、鋭利なニードルチップによるスムーズな穿刺が得られるだけでなく、軽量化され安定した把持が得られる。本デバイスの新たな技術革新は患者ストレスの軽減に寄与する可能性もあり、今後の使用成績が期待される。当施設におけるVABにおけるBD EleVationの使用経験を概説する。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Recently, trifluridine/tipiracil (FTD/TPI) treatment was established as a later-line treatment for metastatic colorectal cancer (mCRC). However, FTD/TPI treatment is frequently associated with hematological toxicity. The aim of this study was to evaluate the efficacy and safety of FTD/TPI in elderly patients with mCRC in a real-world setting. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 74 patients with mCRC who were treated with FTD/TPI. RESULTS: The treatment effect of the elderly patient group was not inferior to that of the younger patient group. Although the incidence of hematological toxicity in the elderly patient group was higher than that in the younger patient group, there were no significant differences in the rate of treatment discontinuation due to adverse events between the two groups. CONCLUSION: In elderly patients with mCRC, FTD/TPI treatment was effective for prolonging survival. However, it should be noted that elderly patients showed a higher rate of hematological toxicity than younger patients.

DOI： 10.21873/anticanres.15440

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: In the Response Evaluation Criteria for Solid Tumors (RECIST) diagnostic criteria, the concepts of progression by preexisting disease (PPL) and progression by new metastases (PNM) have been proposed to distinguish between the progression types of cancer refractory to treatment. According to the tumor biology of cancer progression forms, the "PPL" form indicates invasion, and the "PNM" form indicates metastasis. On the other hand, recent studies have focused on the clinical importance of inflammatory markers as indicators of the systemic tumor immune response. In particular, absolute lymphocyte count (ALC) is an indicator of the host's immune response. Thus, we developed a new measure that combined progression form with ALC. In this study, we clinically validated the combined assessment of progression form and ALC in eribulin chemotherapy. METHODS: From August 2011 to April 2019, a total of 486 patients with locally advanced or metastatic breast cancer (MBC) underwent treatment. In this study, only 88 patients who underwent chemotherapy using eribulin were included. The antitumor effect was evaluated based on the RECIST criteria, version 1.1. To measure ALC, peripheral blood samples collected before eribulin treatment were used. The cut-off value for ALC in this study was 1500/μl, based on previous studies. RESULTS: The PPL group (71 patients, 80.7%) had significantly longer progression-free survival (PFS) (p = 0.022, log-rank) and overall survival (OS) (p < 0.001, log-rank) than the PNM group (17 patients, 19.3%). In the 51 patients with ALC < 1500/μl, the PPL group had a significantly better prognosis than the PNM group (PFS: p = 0.035, OS: p < 0.001, log-rank, respectively). On the other hand, in the 37 patients with ALC ≥ 1500/μl, the PPL group had a better OS compared with the PNM group (p = 0.055, log-rank), but there was no significant difference in PFS between the two groups (p = 0.541, log-rank). Furthermore, multivariate analysis that validated the effect of OS showed that high ORR and "high-ALC and PPL" were factors for a good prognosis (p < 0.001, HR = 0.321; p = 0.036, HR = 0.290). CONCLUSIONS: The progression form of PNM had a worse prognosis than PPL in patients treated with eribulin. In breast cancer patients with eribulin chemotherapy, good systemic immune status, such as ALC ≥ 1500/μl, was associated with less progression, particularly metastasis, and better prognosis. Furthermore, the biomarker "high-ALC (ALC ≥ 1500/μl) and PPL" was particularly useful as a prognostic marker following eribulin chemotherapy.

DOI： 10.1186/s12957-021-02441-w

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: The identification of risk factors for recurrence after resection of colorectal liver metastasis is necessary in order to establish a more effective treatment strategy. In addition to well-known prognostic factors, such as the tumor diameter and number of metastatic tumors, a large amount of intraoperative blood loss (IBL) and blood transfusion have recently been reported to be associated with shorter long-term survival. The aim of this study was to assess the impact of IBL and blood transfusion on the prognosis of colorectal liver metastasis after curative resection. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastasis were enrolled in this study. RESULTS: The high-IBL (>300 ml) group had significantly shorter relapse-free survival after hepatic resection in comparison to the low-IBL (≤300 ml) group (p=0.0025). Patients with blood transfusion had significantly shorter relapse-free survival after hepatic resection in comparison to patients without blood transfusion (p=0.0026). CONCLUSION: A large amount of IBL and blood transfusion may have a negative impact on long-term survival in patients who undergo hepatic resection for colorectal liver metastasis.

DOI： 10.21873/anticanres.15377

PubMed

International / domestic magazine：International journal  

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a group of chronic relapsing inflammatory conditions. Although IgG4-RD can occur in various organs, it is rarely observed in mammary glands. Here, we report a case of IgG4-related mastitis (IgG4-RM) that needed to be differentiated from breast cancer. A 54-year-old woman was examined for a tumor in her left breast. Mammary ultrasonography revealed an irregular hypoechoic tumor measuring 45.0 × 43.0 × 32.0 mm in size. A core-needle biopsy of the left breast tissue revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis. IgG4-RD was diagnosed based on hematological examination that revealed an abnormal IgG4 value of 332 mg/dl. All the clinical diagnostic criteria for IgG4 were met, resulting in a definitive diagnosis of IgG4-RM.

DOI： 10.1093/jscr/rjaa240

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

<sec><title>PURPOSE</title> The molecular subtype of breast cancer is an important component of establishing the appropriate treatment strategy. In clinical practice, molecular subtypes are determined by receptor expressions. In this study, we developed a model using deep learning to determine receptor expressions from mammograms.

</sec><sec><title>METHODS</title> A developing data set and a test data set were generated from mammograms from the affected side of patients who were pathologically diagnosed with breast cancer from January 2006 through December 2016 and from January 2017 through December 2017, respectively. The developing data sets were used to train and validate the DL-based model with five-fold cross-validation for classifying expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2-neu (HER2). The area under the curves (AUCs) for each receptor were evaluated with the independent test data set.

</sec><sec><title>RESULTS</title> The developing data set and the test data set included 1,448 images (997 ER-positive and 386 ER-negative, 641 PgR-positive and 695 PgR-negative, and 220 HER2-enriched and 1,109 non–HER2-enriched) and 225 images (176 ER-positive and 40 ER-negative, 101 PgR-positive and 117 PgR-negative, and 53 HER2-enriched and 165 non–HER2-enriched), respectively. The AUC of ER-positive or -negative in the test data set was 0.67 (0.58-0.76), the AUC of PgR-positive or -negative was 0.61 (0.53-0.68), and the AUC of HER2-enriched or non–HER2-enriched was 0.75 (0.68-0.82).

</sec><sec><title>CONCLUSION</title> The DL-based model effectively classified the receptor expressions from the mammograms. Applying the DL-based model to predict breast cancer classification with a noninvasive approach would have additive value to patients.

</sec>

DOI： 10.1200/PO.20.00176

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

PURPOSE: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors' immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. METHODS: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient's height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and < 30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014. RESULTS: The median BMI was 21.9 kg/m2 (range, 14.3-38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031). CONCLUSIONS: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

DOI： 10.1186/s12885-021-08857-7

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.

DOI： 10.21873/anticanres.15315

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Blood transfusion and a large amount of intraoperative blood loss (IBL) have been reported to have a negative impact on long-term survival via immunosuppression. In recent years, thanks to the spread of laparoscopic surgery and the development of surgical devices, the average amount of IBL has decreased, as has the need for perioperative blood transfusion. Under such conditions, the prognostic significance of the amount of IBL is unclear. The aim of this study was to assess the impact of the amount of IBL on long-term survival. PATIENTS AND METHODS: A total of 277 patients who underwent laparoscopic surgery for stage II/III colorectal cancer were enrolled. RESULTS: The median amount of IBL was 30 ml, and 16 patients received blood transfusion. The overall survival rates were significantly better in the low-IBL (≤100 ml) group than in the high-IBL (>100 ml) group regardless of the blood transfusion. As the amount of IBL increased, the decline rate of the peripheral lymphocyte count increased. CONCLUSION: A large amount of IBL was associated with poor long-term survival, regardless of blood transfusion, in patients with colorectal cancer.

DOI： 10.21873/anticanres.15264

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: The tumor microenvironment plays an important role in tumor progression. Tumor-associated macrophages (TAMs) have been reported to promote proliferation, invasion, metastasis, angiogenesis, and immunosuppression. Furthermore, angiogenesis has been reported to induce chemoresistance due to the inefficient distribution of drugs to cancer cells. However, the impact of TAMs on chemoresistance via angiogenesis in colorectal cancer (CRC) remains unclear. The aim of the study was to evaluate the impact of TAMs on the chemotherapeutic outcome in CRC. PATIENTS AND METHODS: We enrolled 54 patients who underwent chemotherapy for unresectable metastatic CRC after resection of the primary tumor. We evaluated the density of TAMs and the degree of angiogenesis by immunohistochemistry and then explored the correlation between the density of TAMs and chemotherapeutic outcome. Furthermore, we assessed any correlation between the density of TAMs and that of neovascularity. RESULTS: The high-TAMs group had a significantly worse progression-free survival (p=0.0006) and a poorer response rate (p=0.0274) than the low-TAMs group. In addition, a positive correlation was observed between the density of TAMs and the degree of neovascularity (r=0.665, p=0.0004). CONCLUSION: TAMs were shown to promote chemoresistance via angiogenesis in CRC.

DOI： 10.21873/anticanres.15253

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: The aim of this study was to investigate the efficacy and safety of adjuvant chemotherapy in elderly patients with stage III colorectal cancer in a real-world setting. PATIENTS AND METHODS: A total of 165 patients of ≥70 years of age with stage III colorectal cancer who underwent a curative operation between 2008 and 2020 were enrolled in this study. RESULTS: Among septuagenarians, the relapse-free and overall survival rates in the single-agent therapy group and the combination therapy group were significantly better than those in the group treated by surgery alone. However, no significant differences were observed in the relapse-free and overall survival rates of the single-agent therapy group and the combination therapy group. Among octogenarians in whom all regimens were single-agent therapy, adjuvant chemotherapy tended to improve the relapse-free and overall survival rates but not the time to recurrence or cancer-specific survival. CONCLUSION: Single-agent adjuvant chemotherapy may be a useful treatment option for septuagenarians with stage III colorectal cancer. However, the efficacy of adjuvant chemotherapy in octogenarians was not shown in this study.

DOI： 10.21873/anticanres.15150

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: No biomarkers that predict the benefit from anti-vascular endothelial growth factor (VEGF) antibodies have been identified. It is necessary to discover biomarkers that can identify patients who are more likely to benefit from bevacizumab-containing treatment, especially those who are more likely to benefit from treatment with bevacizumab beyond progression (BBP). Levels of serum lactate dehydrogenase (LDH), reported to be an indirect marker of hypoxia and angiogenesis, may be a useful marker for monitoring the efficacy of suppression of angiogenesis. PATIENTS AND METHODS: The clinical data of 91 patients with unresectable metastatic colorectal cancer who were treated with bevacizumab-containing chemotherapy as first-line treatment were collected and studied. RESULTS: In the second-line treatment, the bevacizumab plus chemotherapy group showed significantly better progression-free survival (PFS) in comparison to the chemotherapy-alone group in patients with low post-first-line-treatment serum LDH levels. On the other hand, no significant differences in the PFS rate were observed between the two groups in patients with high post-first-line-treatment serum LDH levels. CONCLUSION: The post-first-line-treatment serum LDH levels may, therefore, be useful marker for predicting the efficacy of treatment with BBP.

DOI： 10.21873/anticanres.15141

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2- breast cancer. METHODS: In stages I-II of HR+/HER2- breast cancer patients who underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy), forty-two patients relapsed after surgery. TILs were evaluated using needle biopsy specimens for the diagnosis of breast cancer. Morphological assessment was conducted using conventional hematoxylin and eosin staining. RESULTS: Six patients had no TILs density. In them, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2- breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144). CONCLUSIONS: Our findings indicate that TILs may predict distant metastatic recurrence in stages I-II of HR+/HER2- breast cancer in patients who do not undergo chemotherapy.

DOI： 10.1186/s12905-021-01373-7

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Recently, elevated levels of postoperative inflammatory markers have been reported to be associated with poorer long-term survival outcomes, regardless of the occurrence of infectious complications, in gastroenterological malignancies. The aim of this study was to evaluate the association between postoperative inflammation and shorter long-term survival after resection of colorectal liver metastases. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastases were enrolled. The CRPmax levels were defined as the highest postoperative serum C-reactive protein levels during hospital stay. RESULTS: The high-CRPmax group had a significantly lower relapse-free survival rate than the low-CRPmax group, regardless of the occurrence of infectious complications. CONCLUSION: In colorectal liver metastasis as well as other malignancies, elevated postoperative levels of serum C-reactive protein are associated with shorter long-term survival, regardless of the occurrence of infectious complications.

DOI： 10.21873/anticanres.15040

PubMed

International / domestic magazine：International journal  

Mammary Paget's disease is a rare malignancy. Mastectomy or breast-conserving surgery has been considered as the standard treatment, while there have been few reports of neoadjuvant chemotherapy (NAC). A 53-year-old woman with erythema and skin ulceration of the left breast was admitted to our institution. Breast examinations revealed left invasive ductal carcinoma (cT1bN0M0, cStage I), and a punch biopsy of the left mammary erythema indicated Paget's disease (cTisN0M0, cStage0). The patient received NAC because of multiple lesions. Consequently, the breast tumor clinically disappeared, and the erythema improved. These outcomes made it easier to perform surgery (left mastectomy and sentinel node biopsy). Histopathological examination revealed no residual cancer cells in either the mammary gland or breast skin, and no metastasis was found in the sentinel lymph node. Therefore, NAC may be a useful treatment for mammary Paget's disease.

DOI： 10.1159/000516762

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

PURPOSE: To demonstrate how artificial intelligence (AI) can expand radiologists' capacity, we visualized the features of invasive ductal carcinomas (IDCs) that our algorithm, developed and validated for basic pathological classification on mammograms, had focused on. MATERIALS AND METHODS: IDC datasets were built using mammograms from patients diagnosed with IDCs from January 2006 to December 2017. The developing dataset was used to train and validate a VGG-16 deep learning (DL) network. The true positives (TPs) and accuracy of the algorithm were externally evaluated using the test dataset. A visualization technique was applied to the algorithm to determine which malignant findings on mammograms were revealed. RESULTS: The datasets were split into a developing dataset (988 images) and a test dataset (131 images). The proposed algorithm diagnosed 62 TPs with an accuracy of 0.61-0.70. The visualization of features on the mammograms revealed that the tubule forming, solid, and scirrhous types of IDCs exhibited visible features on the surroundings, corners of the masses, and architectural distortions, respectively. CONCLUSION: We successfully showed that features isolated by a DL-based algorithm trained to classify IDCs were indeed those known to be associated with each pathology. Thus, using AI can expand the capacity of radiologists through the discovery of previously unknown findings.

DOI： 10.1007/s11604-020-01070-9

PubMed

Other URL： http://link.springer.com/article/10.1007/s11604-020-01070-9/fulltext.html

マンモグラム上での浸潤性乳管癌(IDC)の病理分類のため、深層学習(DL)をベースとしたアルゴリズムの開発と検証に人工知能(AI)を適用し、その有用性について検討した。なお、学習データセットは2006年1月～2016年12月までの期間内に、当院で乳癌と診断された患者529例(年齢25～97歳)から得たマンモグラフィ画像988画像を用いて作成した。VGG-16DLネットワークにより、学習データセットと検証データセットを作成し、テストデータセットには2017年1月～2017年12月までの期間内に、乳癌と診断された当院患者67例(年齢40～92歳)から得た131画像を用いて作成し、アルゴリズムの真陽性と正確さを判定した。可視化技術をアルゴリズムに適用し、マンモグラム上で判明した悪性所見を調査した結果、DLベースのアルゴリズムにより、62画像の真陽性が0.61～0.70の正確さで診断され、マンモグラム上で認められた特徴の可視化により、腺管形成型、充実型および硬性型のIDCが、それぞれ腫瘤の周囲組織や乳腺の歪み、構築の乱れ等、可視化される特徴で描出されることが確認された。以上の所見から、DLベースのアルゴリズムにより、各分類でIDC病理との関連性が指摘されている画像特徴が抽出され、AIの適用により、これまで不明であった所見が明らかにされた。

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: The neutrophil-to-lymphocyte ratio (NLR) and the density of tumor-infiltrating lymphocytes (TILs) have been reported as immunological prognostic factors for various cancers. We evaluated the association between the prognosis and the immunological status in patients who underwent complete resection of pulmonary metastases of colorectal cancer (CRC). PATIENTS AND METHODS: We evaluated the associations between the NLR before the resection of pulmonary metastases and the relapse-free survival (RFS) or overall survival (OS), or between the density of TILs in the pulmonary metastasis and the RFS or OS. RESULTS: The RFS and OS were significantly worse in the NLR-High group than in the NLR-Low group. The RFS was significantly longer in the CD3+TILs-High group than in the CD3+TILs-Low group. CONCLUSION: The NLR and the density of TILs may have prognostic significance in patients who undergo complete resection of pulmonary metastases of CRC.

DOI： 10.21873/invivo.12354

PubMed

症例は52歳、女性。6ヵ月前より右乳房痛と乳腺腫瘤を自覚していたが放置していた。徐々に増大を認めたため近医を受診した。針生検にて境界悪性も否定できない葉状腫瘍と診断されたため、加療目的に当科に紹介となった。初診時、約15cmの右乳腺腫瘤を認め、乳房全体にうっ血は認めるものの明らかな皮膚浸潤は認めなかった。乳腺超音波検査ではプローブを越える内部不均質で血流シグナル豊富な腫瘤を認めた。また、腋窩リンパ節は中心高エコーを認めるものの皮質の肥厚した類円形であった。腋窩リンパ節に対する細胞診では異型細胞を認めた。胸腹部CT検査にて遠隔転移はないものの、超音波検査と同様に右腋窩に腫大したリンパ節を認めリンパ節転移が疑われた。全身麻酔下に乳房切除と腫大したリンパ節をサンプリングした。病理組織診断の結果、悪性葉状腫瘍と診断され、リンパ節転移と診断された。術後1ヵ月で皮下腫瘤を認め、胸部CT検査で多発皮下腫瘤と肺に結節を指摘された。皮下腫瘤を含む胸壁照射(45Gy)施行し、その後ドキソルビシンを2コース施行するも肺結節の増大と胸水貯留を認め、皮下腫瘤の増大も認めた。エリブリンメシル酸塩に変更して治療するも奏効せず、術後5ヵ月で死亡した。非常にまれなリンパ節転移を伴い、集学的治療を行うも急速な増悪を来した悪性葉状腫瘍を経験したため、若干の文献を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>Anaplastic thyroid cancer (ATC) is a rarely occurring refractory disease. While recent clinical trials have demonstrated the efficacy of tyrosine kinase inhibitor (TKI) therapy for ATC, evidence is scarce in clinical practice. In this study, we reviewed our initial experiences with TKI treatment in ATC patients with the aim of revealing the efficacy and safety of the same in clinical practice. We retrospectively reviewed our experiences with TKI treatment use in ATC patients diagnosed at our institute from 2014 to 2019. Changes in the patients’ neutrophil-to-lymphocyte ratio (NLR) by TKI therapy introduction as well as their clinical factors to indicate the efficacy were examined. Seven patients showed no indication for TKI treatment, while 13 (65%) received treatment. The median duration of TKI treatment was 1.9 months. All patients died, and the overall survival period from diagnosis was 4.7 (95% confidence interval: 2.0–11.5) months. Adverse events ≥Grade 3 were observed commonly (92.3%), and resulted in the termination of TKI treatment in six cases (46.1%). Existence of multiple unfavorable characteristics (higher Prognostic Index) was associated with poor survival. The NLR decreased after the introduction of TKIs and increased again when treatment failed. The response rate to TKI among the ATC patients were approximately 30% in practice. Although the duration of the response was short, several patients demonstrated long survival durations when TKI treatment was provided after successful multidisciplinary treatment to control local disease. Decreases in high NLR values during treatment may suggest the continued effect of TKIs.</p>

DOI： 10.1507/endocrj.EJ20-0287

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Angiosarcoma is a malignant mesenchymal tumor characterized by the presence of vascular endothelial cells. Although rare, angiosarcoma developing in the mammary glands has a poor prognosis. We report a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer. A 78-year-old woman noticed a tumor in her right breast and visited our hospital. The patient had undergone breast-conserving surgery and axillary lymph node dissection from the right breast 12 years before the visit. The tumor was diagnosed as T4bN0M0, stage IIIB. Anastrozole was administered as postoperative adjuvant therapy for 5 years; the patient also received 50-Gy whole-breast radiation therapy after surgery. Physical examination during her visit revealed an elevated lesion with blue purpura around the nipple in the right breast. We performed breast ultrasound and detected a well-defined 19.6 × 16.4 × 10.7 mm hypoechoic tumor in the left subareolar area. The patient underwent core needle biopsy (CNB). Based on the CNB specimen findings, she was suspected to experience late local recurrence after surgery. Therefore, she underwent total mastectomy after breast-conserving surgery. A dark-red tumor sized 18 × 12 mm was found in a specimen from the nipple. The pathological diagnosis of the specimen revealed short spindle-shaped tumor cells with strong nuclear pleomorphism and a significant interstitial fibrosis. Immunohistochemistry using D2-40 and CD31 antibodies showed irregular luminal proliferation at the anastomosis, infiltration into the surrounding tissue, and massive necrosis, thereby leading to the diagnosis of breast angiosarcoma. We have reported a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer.

DOI： 10.1159/000513906

PubMed

当院での自験例を後向きに解析し、甲状腺未分化癌(ATC)に対するチロシンキナーゼ阻害剤(TKI)治療の有効性と安全性を評価した。TKI治療導入による患者の好中球/リンパ球比(NLR)の変化と、有効性を表す各種臨床的因子を調べた。その結果、ATC患者20名中7名には病態進行のためTKI治療が適応とならず、13名(65%、男性4名、女性9名、年齢中央値74歳)がTKI治療を受けた。TKI治療期間の中央値は1.9ヵ月であった。全例が死亡し、診断からの全生存期間は4.7ヵ月(95%CI 2.0～11.5)であった。グレード3以上の有害事象が92.3%で認められ、6名(46.1%)は有害事象によりTKI治療が中止された。複数の好ましくない特性(Prognostic Indexが高い)は生存率低下と関連していた。NLRは、TKI導入後に低下し、治療が失敗すると再び上昇した。ATC患者のTKIによる奏効率は、臨床では約30%であった。これらの結果から、奏効期間は短かったが、局所病変を管理するための集学的治療が成功した後にTKI治療が行われた場合、長い生存期間となることが示された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status. However, recent investigations have demonstrated that intratumoral fibrosis is important as a factor affecting the infiltration of TILs. This study investigated the organ specificities of TIL infiltration and intratumoral fibrosis in primary colorectal cancer and distant metastases, as well as the relationship between the distribution of TILs and intratumoral fibrosis. METHODS: Patients who underwent resection of primary tumors or distant metastases for colorectal cancer with distant metastases were enrolled. We evaluated the TIL infiltration by immunohistochemical staining with CD3&CD8 and intratumoral fibrosis by immunohistochemical staining with α-SMA positive cancer-associated fibroblasts and Masson's trichrome staining against collagen fibers. The "ImageJ" was used to evaluate fibrosis, and the density of TILs in the dense and sparse areas of fibrosis was calculated. The Immunoscore (IS) was obtained based on the density of CD3+/CD8+TILs in the tumor center and invasive margin of the primary tumor. RESULTS: The degree of CD3+/CD8+TIL infiltration in peritoneal metastases was significantly lower than that in liver and lung metastases. The area ratio of α-SMA positive cancer-associated fibroblasts and collagen fibers in peritoneal metastases was significantly higher than that of liver and lung metastases. Furthermore, the density of TILs in the high-fibrosis area was significantly lower than that in the low-fibrosis area. In the high-IS group of primary tumors, the degree of TIL infiltration in distant metastases was significantly higher than that in the low-IS group. CONCLUSION: The infiltration of T lymphocytes into tumors is prevented in peritoneal metastases of colorectal cancer due to the high intratumoral fibrosis, which may lead to treatment resistance and a poor prognosis.

DOI： 10.1371/journal.pone.0255049

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. METHODS: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. RESULTS: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. CONCLUSIONS: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

DOI： 10.1186/s12885-020-07673-9

PubMed

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

BACKGROUND: The peripheral blood neutrophil-lymphocyte ratio(NLR), platelet-lymphocyte ratio(PLR), and lymphocyte- monocyte ratio(LMR)of cancer patients have been proposed as indicators of systemic inflammatory response. Recombinant human-soluble thrombomodulin(rTM)has also been reported its efficacy in DIC associated with solid tumors. In this study, we investigated the clinical significance of inflammatory markers in rTM therapy for DIC associated with solid tumors. PATIENTS AND METHOD: A retrospective study of 63 patients with solid tumors with DIC was performed. We examined the correlation between NLR, LMR, PLR and DIC withdrawal rate and 28-day survival rate. RESULTS: The DIC withdrawal rate was not correlated in LMR(p=0.655), and significantly higher in low NLR and low PLR cases(p=0.037, p=0.024). Furthermore, 28-day survival rate was not correlated in LMR(p=0.632), and significantly higher in low NLR and low PLR cases(p= 0.046, p=0.014). CONCLUSIONS: It was suggested that NLR and PLR may be useful as predictive markers of DIC withdrawal rate and 28-day survival rate in rTM therapy for DIC associated with solid tumors.

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

The patient was 54 years old, female. She was aware of gradually worsening right peri-eyelid swelling 2 years before the first presentation to our dermatology department. She underwent biopsy of eyelid skin 2 times. Nevertheless, definitive diagnosis was not obtained. Two months after the initial examination, right anterior thoracic swelling appeared, and right axillary, right subclavian, and interpectoral lymphadenopathy were detected. She was referred to our department for diagnosing metastatic breast cancer. Ultrasonography showed hypoechoic lesion with distortion(largest lesion>2 cm)in right breast, which was suspected to be a breast cancer. The results of breast core needle biopsy, the third time's eyelid skin biopsy and additional imaging studies confirmed T2N3M1, Stage Ⅳ right mammary invasive lobular carcinoma with metastasis to the eyelid skin, right axillary lymph nodes, right subclavian lymph nodes and the subcutaneous tissue of the right back. Immunohistochemical studies showed ER-positive, PgR-negative, HER2-negative, and low Ki-67 expression. Endocrine therapy with letrozole was initiated, which maintained stable disease without compromising the quality of life.

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.

PubMed

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 59-year-old female was performed a left mastectomy with axillary lymph node dissection. Final diagnosis of the surgical specimen was left breast cancer pT2N1M0, Stage ⅡB, Luminal type. She was treated with adjuvant endocrine therapy, however, chest wall recurrence was identified at 1 year and 3 months after surgery, and curative resection of this tumor and radiotherapy were performed. Nine months later, she was admitted to the hospital for cervical pain and dyspnea, and magnetic resonance imaging showed bone metastasis in cervical vertebra which compressed spinal cord. Although cervical fusion therapy was performed, she died 39 days later. Metastasis spinal cord compression in breast cancer patients may result in irreversible spinal cord injury if treatment is delayed. Rapid diagnosis and systemic treatment for oncologic emergency are significant.

PubMed

PubMed

症例は56歳、女性。右乳房腫瘤を自覚し近医を受診、精査加療目的にて当院紹介となった。乳腺超音波検査にて右乳腺C領域に約5cm大の腫瘤を認め、針生検にて右乳癌(浸潤性乳管癌、ER陰性、PgR陰性、HER2陰性、Ki-67高発現)との診断に至った。CT検査では、右乳腺腫瘤、右腋窩リンパ節腫大、肝腫瘍、縦隔リンパ節腫大および肺腫瘍が認められた。肺腫瘍に対して気管支鏡下生検を行い、原発性肺癌との診断を得た。また、骨シンチグラフィでは右大腿骨近位部に溶骨性変化が認められた。治療前診断は、肺腺癌、cT2a、N2/3、M1b/1c(HEP、OSS)、Stage III A/B or IVA/B(PD-L1陽性)、右乳癌、T4b、N2、M0/1(HEP、OSS、LYM)、Stage IIIB or IV triple-negative(PD-L1陽性)の重複癌であった。右乳癌に対して局所出血コントロール目的にて手術(単純乳房切除および腋窩リンパ節郭清術)を施行し、その後に全身化学療法(アテゾリズマブ+カルボプラチン+パクリタキセル)を開始したところ、部分奏効が得られた。今回、PD-L1(SP142)陽性肺癌・乳癌重複癌に対してアテゾリズマブ併用療法が奏効した1例を経験した。(著者抄録)

症例は59歳、女性。左乳癌に対して左乳房切除術および腋窩リンパ節郭清術を施行した。最終診断はpT2N1M0、Stage IIB、ER強陽性、PgR陰性、HER2陰性であった。補助内分泌療法を施行していたが、1年3ヵ月後に左胸壁再発を認めたため局所切除術および放射線照射を施行した。再発手術より9ヵ月後、呼吸困難と頸部痛を主訴に救急搬送となり、精査の結果、乳癌頸椎転移による軸椎歯突起骨折および頸髄の圧迫を認めた。早期にC1-C2固定術を施行したが、全身状態の増悪を来し、固定術より39日後に死亡した。乳癌脊椎転移のうち脊髄圧迫症状を有する症例では、治療介入のタイミングを逸すると不可逆的な脊髄障害に至るためoncologic emergencyとして治療前診断を勧め、迅速に全身療法を開始することが望まれる。(著者抄録)

背景:近年、担癌患者の末梢血の好中球・リンパ球比(NLR)、血小板・リンパ球比(PLR)、リンパ球・単球比(LMR)などが全身性炎症性反応を評価する指標として、種々の癌腫において報告されている。一方で、遺伝子組換えヒトトロンボモジュリン製剤(rTM)の固形癌DICに対する有用性が散見されるようになった。本研究では、固形癌DICに対するrTM療法における全身性炎症性マーカーの臨床的意義を検討した。対象と方法:DIC症例に対してrTMを投与した固形癌患者63例を対象とし、NLR、LMR、PLRとDIC離脱率および28日生存率との相関を確認した。結果:DIC離脱率との検討では、LMRで相関はなく(p=0.655)、低NLR症例や低PLR症例では有意に離脱率が高かった(p=0.037、p=0.024)。さらに28日生存率との検討においてもLMRでは相関はなく(p=0.632)、低NLR症例や低PLR症例では有意に28日生存率が高かった(p=0.046、p=0.014)。結語:NLRおよびPLRは固形癌DICに対するrTM療法において、DIC離脱率や28日生存率の予後予測マーカーとして有用性が示唆された。(著者抄録)

症例は54歳、女性。初診2年前から右眼瞼周囲皮膚腫脹が徐々に増悪し、当院皮膚科で眼瞼皮膚生検を2回行うも確定診断に至らなかった。初診後2ヵ月で右前胸部腫脹が出現し、右腋窩・右鎖骨下・右大胸筋小胸筋間にリンパ節腫大を認め、乳癌による転移が疑われたため当科紹介となった。乳腺超音波検査の結果、右乳房CD領域に2cm大の乳癌を疑う低エコー域を認めた。当科での精査および3回目の眼瞼皮膚生検の結果より、右乳腺浸潤性小葉癌の眼瞼皮膚転移、右腋窩・右鎖骨下リンパ節転移、右背部皮下転移、T2N3M1、Stage IVと診断した。ER陽性、PgR陰性、HER2陰性、Ki-67低発現であり、レトロゾールの内服を開始した。現在もSDを維持しており、QOLが低下することなく治療を継続している。(著者抄録)

症例は70歳、女性。3年前より右乳房腫瘤を自覚するも、放置していた。増大を認め、出血を伴うようになったために近医を受診し、精査加療目的にて当院紹介となった。来院時、右乳房内上部に約8cm大の易出血性潰瘍を伴う腫瘤が認められた。乳腺超音波検査にて右A区域に約8cm大の腫瘤を確認、針生検にて浸潤性乳管癌(ER強陽性、PgR強陽性、HER2陽性、Ki-67低発現)であった。右腋窩リンパ転移を認めるも遠隔転移はなく、治療前診断は右乳癌、cT4bN1M0、Stage IIIB、Luminal HERであった。ペルツズマブ、トラスツズマブ、ドセタキセルにて化学療法を開始したところ、6サイクル投与で部分奏効が得られた。その後、右乳房全体に発赤を認め、乳癌皮膚転移が疑われた。メトロニダゾールゲル起因性皮膚炎も鑑別とされ、塗布中止としたところ改善が認められた。パッチテストにてメトロニダゾールゲルに対する反応を有し、メトロニダゾールゲル起因性皮膚炎との診断に至った。(著者抄録)

HER2陽性再発乳癌の初期治療は、ペルツズマブ+トラスツズマブ+ドセタキセルが第一選択とされている。しかしドセタキセルは、有害事象の発症も少なくない。症例は48歳、女性。左乳房腫瘤にて受診、精査にて左乳癌(T1N0M0、Stage I、Luminal A)との診断に至った。乳房温存手術およびセンチネルリンパ節生検を施行し、術後は残存乳腺への照射およびタモキシフェンによる補助療法を行った。術後3年6ヵ月に胸壁再発を来したため局所切除を施行した。ここでHER2陽転化が確認されたため、フルオロウラシル、エピルビシン、シクロホスファミド(FEC)およびパクリタキセル+トラスツズマブを開始した。トラスツズマブ単独投与11 cycle目に肝転移が確認され、ペルツズマブ+トラスツズマブ+ドセタキセルへと変更、最良効果のPRが得られた。その後T-DM1へ移行、5 cycle投与し最良効果はSDであった。ここで肝転移が増悪し、ペルツズマブ+トラスツズマブ+エリブリンへレジメン変更を行った。重篤な有害事象も認めず、肝転移は縮小しPRとなり、現在は20 cycleにて投与を継続している。(著者抄録)

症例は68歳、女性。右乳癌術後の肺転移および局所リンパ節再発に対してエベロリムス+エキセメスタン療法を開始したところ、12週目に間質性肺疾患を発症した。エベロリムスを中止し、ステロイドパルス療法を実施したが重症化し人工呼吸管理に至った。その後、緩徐ではあるものの呼吸状態の改善が認められ、人工呼吸器管理9日後には離脱に成功した。エベロリムスによる間質性肺疾患は軽症例の報告が多く、重症例はまれである。今回、エベロリムスによるびまん性肺胞障害が重症化し、呼吸器管理を要した転移性乳癌を経験したので若干の文献的考察を含めて報告する。(著者抄録)

International / domestic magazine：Domestic journal  

A 68-year-old woman was receiving chemotherapy and endocrine therapy for right breast cancer postoperative pulmonary metastasis and local lymph node recurrence. However, she developed interstitial pneumonia 12 weeks after initiating treatment with everolimus and exemestane. Treatment with everolimus and exemestane was discontinued and steroid pulse therapy was initiated; however, she required ventilator management because of the severity of the pneumonia. The patient's condition improved 9 days after ventilator management. Everolimus-induced interstitial pneumonia is often mild, but it can be severe in rare cases. In our case, everolimus-induced diffuse alveoli damage was successfully treated with ventilator management.

PubMed

J-GLOBAL

Other URL： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J00296&link_issn=&doc_id=20210118600211&doc_link_id=%2Fab8gtkrc%2F2020%2F004713%2F211%2F2370-2372%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2020%2F004713%2F211%2F2370-2372%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Currently, when determining treatment regimens, there is an emphasis on the quality of life (QOL), in addition to treatment efficacy. Especially in hormone receptor-positive breast cancer with distant metastases, unless death is imminent, a common first-line treatment is endocrine therapy, which has fewer side effects. In the present study, the differences in QOL were evaluated based on the age and prognostic indicators of 46 patients with hormone receptor-positive breast cancer with distant metastases (stage IV), who received first-line endocrine therapy at the Osaka City University Hospital (Osaka, Japan) between November 2007 and November 2016. QOL score before and after endocrine therapy was retrospectively analyzed, using the Quality of Life Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-Breast (QOL-ACD-B). There was no significant association between age and any of the clinicopathological features investigated. However, the QOL score of the elderly patient group was significantly higher compared with that of the younger group in the 'Satisfaction with treatment and coping with disease' subcategory (P=0.008). The QOL score of the younger age group in the same subcategory was significantly improved by the treatment (P=0.013). The patients that had an increased overall QOL score 3 months after treatment initiation had a significant extension of progression-free survival (PFS) rate compared to the patients with decreased or no change in QOL (P=0.032). In conclusion, psychological stress was more prominent in younger patients with stage IV breast cancer treated with hormonal therapy compared with elderly patients. Importantly, improving QOL within the 3 months after treatment initiation could lead to longer PFS rate.

DOI： 10.3892/ol.2020.12041

PubMed

J-GLOBAL

J-GLOBAL

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses may be evaluated by measuring tumor-infiltrating lymphocytes (TILs), which has been frequently verified clinically. In the present study, the prediction of the therapeutic effect of endocrine therapy by TILs on stage IV breast cancer was clinically analyzed. Data from 40 patients who underwent endocrine therapy as the initial drug therapy for stage IV breast cancer were used. The correlation between TILs, evaluated according to standard methods, and prognosis, including the efficacy of endocrine therapy, was investigated retrospectively. Patients with ≥50% lymphocytic infiltration were considered to have lymphocyte-predominant breast cancer (LPBC). An analysis of outcomes revealed no difference in progression-free survival (PFS; P=0.171), time to treatment failure (TTF; P=0.054), or overall survival (OS; P=0.641) between the high TIL (>10%) and low TIL (≤10%) groups. Patients with LPBC (≥50%) exhibited a significant prolongation of PFS (P=0.005, log-rank), TTF (P=0.001) and OS (P=0.027) compared with non-LPBC patients. On receiver operating characteristics (ROC) curve analysis, better results were obtained with LPBCs [area under the curve (AUC)=0.700] than with TILs (AUC=0.606). The present findings suggest that a high level of lymphocytic infiltration in the tumor stroma may serve as a predictor of the therapeutic efficacy of endocrine therapy in patients with stage IV estrogen receptor-positive breast cancer.

DOI： 10.3892/mco.2020.2063

PubMed

DOI： 10.21873/anticanres.14415

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Infusion reactions (IRs) often occur with trastuzumab. Although premedication by non-steroidal anti-inflammatory drugs can be effective to a certain extent, IRs are still common and infrequently severe. Therefore, a predictive marker that can select patients requiring further prophylaxis is useful for appropriate prevention, but remains unclear. PATIENTS AND METHODS: We conducted a retrospective analysis for 136 consecutive female inpatients aged 18 years and older who received 8 mg/kg of the initial trastuzumab administration for breast cancer with a 25-mg dose of rectal diclofenac before trastuzumab infusion between May 2007 and April 2019, in order to assess IRs. RESULTS: Overall, 57 patients were eligible for inclusion in the study. IRs were observed in 17.5% (10/57) of the patients. Univariate analysis showed that patients with a low eosinophil percentage (≤2%) were associated with IRs (p=0.016). CONCLUSION: A low eosinophil percentage can be a useful new predictive marker for trastuzumab-induced IRs in patients with breast cancer.

DOI： 10.21873/anticanres.14401

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer. METHODS: We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter > 2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted. RESULTS: For SLN biopsy (SLNB), a median of 2 (range, 1-8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter > 10 mm than in those with diameter ≤ 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p < 0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p = 0.017, lymphatic invasion; p = 0.002). Multivariate analysis for SLNM predictors revealed lymphatic invasion (p = 0.008, odds ratio [OR] = 2.522) and TILs (p < 0.001, OR = 0.137) as independent factors. CONCLUSIONS: Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.

DOI： 10.1186/s12885-020-07101-y

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperatively diagnosed by CNB as DCIS. Risk factors for invasion have been studied by postoperative examination, but no factors have been found that could be obtained preoperatively from blood tests. In this study, we investigated factors predictive of invasion based on preoperative blood tests in patients diagnosed with DCIS by preoperative biopsy. METHODS: In this study, 118 patients who were diagnosed with DCIS by preoperative biopsy were included. Biopsies were performed with 16-gauge CNB or VAB. Peripheral blood was obtained at the time of diagnosis. This study evaluated absolute platelet count, absolute lymphocyte count, lactate dehydrogenase, carcinoembryonic antigen, and cancer antigen 15-3 (CA15-3). The platelet-lymphocyte ratio (PLR) was calculated by dividing the absolute platelet count by the absolute lymphocyte count, and patients were grouped into high PLR (≥160.0) and low PLR (< 160.0) groups. RESULTS: Invasion was found more frequently after surgery in pathologically high-grade cases than in pathologically not-high-grade cases (p = 0.015). The median PLR was 138.9 and 48 patients (40.7%) were classified into the high PLR group. The high PLR group was significantly more likely to have invasion detected by the postoperative pathology than the low PLR group (p = 0.018). In multivariate analysis of factors predictive of invasion in postoperative pathology, a high PLR (p = 0.006, odds ratio [OR] = 3.526) and biopsy method (VAB vs. CNB, p = 0.001, OR = 0.201) was an independent risk factor. CONCLUSIONS: The PLR may be a predictor of invasion in the postoperative pathology for patients diagnosed with DCIS by preoperative biopsy.

DOI： 10.1186/s12885-020-07001-1

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: In addition to its cytocidal effects as a microtubule dynamics inhibitor, eribulin mesylate (eribulin) regulates the tumour microenvironment. We examined the clinical significance of tumour infiltrating lymphocytes (TILs) and transforming growth factor-β (TGF-β), which are local markers of host immunity, and of the neutrophil-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC), which are systemic markers. PATIENTS AND METHODS: We administered eribulin chemotherapy to 106 patients with locally advanced or metastatic breast cancer. Of these, 21 had their lesions resected. RESULTS: The response to eribulin was significantly associated with ALC (p=0.007). The expression of pSmad2 (an indicator of activation of TGF-β downstream signaling) was significantly decreased before and after eribulin chemotherapy (p<0.001). Moreover, a baseline ALC ≥ 1,500 /μl was observed in a significantly high number of patients with pSmad2 negative conversion (p<0.001). CONCLUSION: Eribulin improved the tumour immune microenvironment by decreasing TGF-β expression. This demonstrated that local change can be evaluated based on ALC.

DOI： 10.21873/anticanres.14317

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence. METHODS: This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined. RESULTS: When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p = 0.024). CONCLUSIONS: Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

DOI： 10.1186/s12967-020-02307-x

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: The host's systemic inflammatory response is thought to affect the progression of cancer and the antitumor effects of chemotherapy. Meta-analyses have reported that the peripheral blood platelet-to-lymphocyte ratio (PLR) is a prognostic indicator of this effect. Therefore, we hypothesized that PLR may differ, depending on sentinel lymph node metastasis (SLNM) in patients diagnosed with cT1N0M0 breast cancer by preoperative imaging. This study investigated the ability of preoperative PLR to predict SLNM in patients diagnosed with cT1N0M0 breast cancer. PATIENTS AND METHODS: This study included 475 patients with cT1N0M0 breast cancer diagnosed by preoperative imaging. Peripheral blood was obtained at diagnosis, i.e., before surgery. PLR was calculated from preoperative blood tests, by dividing the absolute platelet count by the absolute lymphocyte count. RESULTS: The probability of SLNM was significantly higher (p=0.002) in cases where the tumor diameter was larger than 10 mm. The incidence of SLNM was significantly high in the high (preoperative) PLR group (p=0.031). Multivariate analysis revealed that high PLR [compared to low PLR, p=0.021, odds ratio (OR)=1.815, 95% confidence interval (CI)=1.093-3.090] and large tumor size (compared to small tumor size, p=0.001, OR=2.688, 95%CI=1.524-4.997) were independent factors influencing SLNM. CONCLUSION: PLR may act as a predictor of SLNM in cT1N0M0 breast cancer.

DOI： 10.21873/anticanres.14202

PubMed

DOI： 10.1159/000506979

PubMed

Publishing type：Research paper (scientific journal)  

進行乳癌の治療において、全生存期間(OS)benefitを有する薬剤選択肢は限定されている。エリブリンは国際第III相試験でOS延長が認められた薬剤であるが、癌微小環境調整作用がその機序にかかわっているものと考えられている。一方で、治療に伴うbiology変化はbreast cancer subtype discordanceとして知られている。今回、エリブリン化学療法によりbiology変化を来した進行乳癌の1例を経験したので報告する。症例は54歳、女性。左乳房にしこりを自覚し近医を受診、精査加療目的に当院を受診した。超音波検査では、左乳腺C区域を主座とした巨大腫瘤を認め、腋窩に癒合する腫大したリンパ節を認めた。針生検にて浸潤性乳管癌(ER強陽性、PgR陰性、HER2陰性、Ki-67低発現)が確認された。CT検査では、多発肺転移が認められた。左進行乳癌、cT4N2M1、stage IV、Luminal Aの診断に対しletrozole投与を行ったが、6ヵ月後に原発巣および腋窩リンパ節の増大を認めた。ここでエリブリン化学療法を開始し部分奏効が得られたが、11 cyclesで腋窩に新規リンパ節転移が出現した。原発巣と腋窩リンパ節の治療効果の乖離が認められたために再生検を施行したところ、主病巣、腋窩リンパ節ともにER強陽性、PgR陰性、HER2陽性、Ki-67低発現とHER2陽転化が認められた。(著者抄録)

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 68-year-old woman noticed a tumor in her left breast and visited our hospital. She was diagnosed with left breast cancer cT2N2M0, stage ⅢA, and surgery was performed after the neoadjuvant chemotherapy. Although this case was indicated for radiation therapy(PMRT)after total mastectomy, postoperative radiation was not performed due to an implantable pacemaker placed in the left anterior chest. Therefore, postoperative adjuvant therapy with endocrine therapy was started. After 3 years of treatment, her left axillary lymph node was enlarged, and needle biopsy confirmed metastasis and recurrence. When local excision was performed, postoperative irradiation was deemed necessary because residual microlesions were suspected. Irradiation planning did not deny the possibility that the pacemaker in the anterior chest indwelling could become the irradia- tion range. Therefore, a leadless pacemaker was inserted, and local irradiation(50 Gy/20 Fr)was performed without complications. The next treatment is fulvestrant, and no recurrence has been observed 6months postoperatively.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

In the treatment of advanced breast cancer, onlya few drugs confer overall survival(OS)benefit. Eribulin is a drug that was shown to extend OS in an international phase Ⅲtrial; however, the underlying mechanism is thought to involve cancer microenvironment regulation. The concept of "breast cancer subtype discordance" implies the biological changes that accompany treatment. Herein, we encountered a case of advanced breast cancer in a 54-year-old woman that showed biological changes after eribulin chemotherapy. The patient noticed a lump in her left breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonographyrevealed a large mass at the center of the left mammarygland and axillaryly mph node swelling. Core-needle biopsyconfirmed an invasive ductal carcinoma(ER stronglypositive, PgRnegative, HER-2 negative, Ki-67 low expression). CT findings showed multiple lung metastases. Letrozole was administered for cT4N2M1, stage Ⅳ, Luminal A, which showed progression to the left side with advances in breast cancer. Six months later, the primarytumor and axillaryly mph nodes showed progression. Subsequent treatment with eribulin was started, and partial response was obtained; however, new lymph node metastasis developed in the axilla after 11 cycles. The primary tumor and axillaryly mph nodes showed stronglypositive ER expression, were PgR-negative and HER2-positive, and showed Ki-67 low expression and HER2-positive conversion.

PubMed

Publishing type：Research paper (scientific journal)  

症例は86歳、女性。左胸壁腫瘤を自覚して近医を受診した。既往としては、32年前に他院で左乳癌に対して左乳房全摘術を施行された。また、約2年前から両肺野に多発小結節を認めており、転移再発も疑われ当院紹介となった。胸腹部CTでは両肺野に多発小結節と、左第2〜3肋間の傍胸骨に胸骨硬化像を伴う腫瘤が認められた。乳腺超音波検査では53mm大の境界明瞭で不整形の低エコー腫瘤として認められ、同部位の針生検を施行した。病理組織学的所見が32年前の手術標本の所見に類似し、ER強陽性、PgR強陽性、HER2陰性、Ki-67低値と32年前と同様のバイオロジーであったため乳癌の晩期再発と診断した。レトロゾールを開始したところ、6ヵ月後に両肺野の多発小結節の一部が増大し進行に至った。現在、二次内分泌療法としてアベマシクリブおよびフルベストラントを投与中である。今回われわれは、術後32年の長期間経過後に転移再発を来した乳癌晩期再発症例を経験したので報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

眼症状を来し失明に至った転移再発乳癌の2例を経験した。症例1は26歳、女性。右乳癌、cT2N1M0、stage IIB、トリプルネガティブに対し術前化学療法後に手術を施行した。術後1年で骨転移や水腎症あり。化学療法を施行するも術後2年目に眼痛と頭痛が出現し、外眼筋への転移を疑われた。両側眼窩に放射線治療を施行したが視力低下が進行し失明、眼症状発症後1ヵ月で死亡した。症例2は42歳、女性。右乳癌、cT4N3M1(骨)、stage IV、トリプルネガティブで化学療法中、複視で眼科を受診した。精査で視神経乳頭腫脹があり癌性髄膜炎によるものが疑われた。徐々に視力低下、失明に至った。眼症状発症後2ヵ月で死亡した。乳癌の眼窩転移はまれである。両症例とも画像上明らかな中枢神経転移は認めなかったが、急激な視力低下から失明に至り、QOL低下が著しかった。若年のトリプルネガティブでは急速な症状進行の可能性があり、注意が必要である。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は68歳、女性。左乳房の腫瘤を自覚し、当院を受診した。精査にて左乳癌、cT2N2M0、stage IIIAと診断し、術前化学療法後(FEC100 followed by wPTX)に手術を施行した(単純乳房切除術および腋窩リンパ節郭清)。乳房全切除後放射線療法(PMRT)の適応であったが、左前胸部に皮下埋め込み型ペースメーカが留置されていたため術後照射は施行せず、内分泌療法による術後補助療法を開始した。開始から3年、左腋窩リンパ節腫大を認め針生検にて再発が確認された。局所切除を行ったところ、微小病変の残存が疑われたため術後照射を要すると考えられた。照射計画を行ったところ、前胸部留置のペースメーカが照射範囲となる可能性が否定できなかった。そのためリードレスペースメーカへの入れ替えを行い、合併症なく局所照射(50Gy/20Fr)を施行し得た。その後、フルベストラントの投与を行い、術後6ヵ月であるが再発は認められていない。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

進行乳癌の治療において、全生存期間(OS)benefitを有する薬剤選択肢は限定されている。エリブリンは国際第III相試験でOS延長が認められた薬剤であるが、癌微小環境調整作用がその機序にかかわっているものと考えられている。一方で、治療に伴うbiology変化はbreast cancer subtype discordanceとして知られている。今回、エリブリン化学療法によりbiology変化を来した進行乳癌の1例を経験したので報告する。症例は54歳、女性。左乳房にしこりを自覚し近医を受診、精査加療目的に当院を受診した。超音波検査では、左乳腺C区域を主座とした巨大腫瘤を認め、腋窩に癒合する腫大したリンパ節を認めた。針生検にて浸潤性乳管癌(ER強陽性、PgR陰性、HER2陰性、Ki-67低発現)が確認された。CT検査では、多発肺転移が認められた。左進行乳癌、cT4N2M1、stage IV、Luminal Aの診断に対しletrozole投与を行ったが、6ヵ月後に原発巣および腋窩リンパ節の増大を認めた。ここでエリブリン化学療法を開始し部分奏効が得られたが、11 cyclesで腋窩に新規リンパ節転移が出現した。原発巣と腋窩リンパ節の治療効果の乖離が認められたために再生検を施行したところ、主病巣、腋窩リンパ節ともにER強陽性、PgR陰性、HER2陽性、Ki-67低発現とHER2陽転化が認められた。(著者抄録)

症例は86歳、女性。左胸壁腫瘤を自覚して近医を受診した。既往としては、32年前に他院で左乳癌に対して左乳房全摘術を施行された。また、約2年前から両肺野に多発小結節を認めており、転移再発も疑われ当院紹介となった。胸腹部CTでは両肺野に多発小結節と、左第2〜3肋間の傍胸骨に胸骨硬化像を伴う腫瘤が認められた。乳腺超音波検査では53mm大の境界明瞭で不整形の低エコー腫瘤として認められ、同部位の針生検を施行した。病理組織学的所見が32年前の手術標本の所見に類似し、ER強陽性、PgR強陽性、HER2陰性、Ki-67低値と32年前と同様のバイオロジーであったため乳癌の晩期再発と診断した。レトロゾールを開始したところ、6ヵ月後に両肺野の多発小結節の一部が増大し進行に至った。現在、二次内分泌療法としてアベマシクリブおよびフルベストラントを投与中である。今回われわれは、術後32年の長期間経過後に転移再発を来した乳癌晩期再発症例を経験したので報告する。(著者抄録)

眼症状を来し失明に至った転移再発乳癌の2例を経験した。症例1は26歳、女性。右乳癌、cT2N1M0、stage IIB、トリプルネガティブに対し術前化学療法後に手術を施行した。術後1年で骨転移や水腎症あり。化学療法を施行するも術後2年目に眼痛と頭痛が出現し、外眼筋への転移を疑われた。両側眼窩に放射線治療を施行したが視力低下が進行し失明、眼症状発症後1ヵ月で死亡した。症例2は42歳、女性。右乳癌、cT4N3M1(骨)、stage IV、トリプルネガティブで化学療法中、複視で眼科を受診した。精査で視神経乳頭腫脹があり癌性髄膜炎によるものが疑われた。徐々に視力低下、失明に至った。眼症状発症後2ヵ月で死亡した。乳癌の眼窩転移はまれである。両症例とも画像上明らかな中枢神経転移は認めなかったが、急激な視力低下から失明に至り、QOL低下が著しかった。若年のトリプルネガティブでは急速な症状進行の可能性があり、注意が必要である。(著者抄録)

J-GLOBAL

J-GLOBAL

J-GLOBAL

Publishing type：Research paper (scientific journal)  

症例は68歳、女性。左乳房の腫瘤を自覚し、当院を受診した。精査にて左乳癌、cT2N2M0、stage IIIAと診断し、術前化学療法後(FEC100 followed by wPTX)に手術を施行した(単純乳房切除術および腋窩リンパ節郭清)。乳房全切除後放射線療法(PMRT)の適応であったが、左前胸部に皮下埋め込み型ペースメーカが留置されていたため術後照射は施行せず、内分泌療法による術後補助療法を開始した。開始から3年、左腋窩リンパ節腫大を認め針生検にて再発が確認された。局所切除を行ったところ、微小病変の残存が疑われたため術後照射を要すると考えられた。照射計画を行ったところ、前胸部留置のペースメーカが照射範囲となる可能性が否定できなかった。そのためリードレスペースメーカへの入れ替えを行い、合併症なく局所照射(50Gy/20Fr)を施行し得た。その後、フルベストラントの投与を行い、術後6ヵ月であるが再発は認められていない。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Anaplastic thyroid cancer (ATC) is a rare refractory disease, frequently associated with BRAF mutations and aberrant vascular endothelial growth factor (VEGF) secretion. The antitumor effects of sorafenib were evaluated, and its mechanisms of action were investigated. Four human ATC cell lines were used: OCUT‑4, which possesses a BRAF mutation; OCUT‑6 and ACT‑1, which carry NRAS mutations; and OCUT‑2, which possesses mutations in BRAF and PI3KCA. The viability of Sorafenib was evaluated by MTT assay. In order to examine the inhibitory effect of Sorafenib on intracellular signal transduction, expression of mitogen‑activated protein kinase kinase was examined by western blotting. In addition, cell cycle analysis was performed using flow cytometry. The inhibitory effects of sorafenib on the growth of ATC cells and human umbilical vein endothelial cells (HUVECs) stimulated with conditioned media from ATC cells were examined. Sorafenib inhibited the viability of OCUT‑4 more effectively than other ATC cell lines; these effects may have been mediated cytostatically by suppressing mitogen‑activated protein kinase kinase phosphorylation. Conversely, similar suppression was not observed in OCUT‑6 cells, which possess an NRAS mutation. The four cell lines secreted different quantities of VEGF, and the proliferation of HUVECs was differentially stimulated by their conditioned media. Both anti‑VEGF antibody and sorafenib prevented this stimulation of proliferation. In conclusion, sorafenib more effectively inhibited RAF‑generated growth signals in ATC cells compared with signals generated by its upstream gene, RAS. ATC cells stimulated the growth of HUVECs via humoral factors, including VEGF; this effect was clearly inhibited by sorafenib. The present findings highlighted the potential of sorafenib for the treatment of ATC and provided insight into its mechanism of action.

DOI： 10.3892/ijo.2019.4881

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: The utility of peripheral blood neutrophil-to-lymphocyte ratios (NLRs) and platelet-to-lymphocyte ratios (PLRs) as prognostic predictors of surgery and chemotherapy in breast cancer has been reported. In this study, NLRs and PLRs were calculated before treatment and during cancer progression in primary hormone receptor-positive breast cancer (HRBC) patients who chose endocrine therapy (ET) as the primary treatment, and prognostic prediction and factor analysis were performed. PATIENTS AND METHODS: A total of 55 patients diagnosed with stage IIIB, IIIC, or IV HRBC who received ET as the primary treatment were included. RESULTS: Increased NLRs were found to significantly contribute to a shorter overall survival from cancer progression (OS-CP) (p=0.040, log-rank). Increased PLRs were similarly associated with a shorter OS-CP (p=0.036, log-rank). In multivariate analysis, an increased NLR was an independent prognostic factor (p=0.035, hazard ratio(HR)=5.221). CONCLUSION: Changes in NLRs and PLRs become prognostic indicators when the therapeutic effect of ET is limited.

DOI： 10.21873/anticanres.13752

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

J-GLOBAL

J-GLOBAL

Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000502949

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/AIM: Eribulin is currently used to treat advanced and metastatic breast cancer in the clinical setting; however, its efficacy is inhibited by resistance acquisition in many cases. Thus, the present study established two eribulin-resistant breast-cancer cell lines, and used these to investigate the mechanisms that underly eribulin-resistance acquisition. MATERIALS AND METHODS: Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin. RESULTS: The eribulin-resistant cells acquired resistance to eribulin, as well as several other anticancer drugs. After eribulin treatment, the eribulin-resistant cell lines showed no morphological change, no increased expression of epithelial-cadherin, nor any significant alteration in cell-cycle distribution. In contrast, the expression levels of programmed death-ligand 1 were increased in the MCF-7/eribulin-resistant compared to MCF-7 cells. CONCLUSION: The herein developed eribulin-resistant cell lines acquired cross-resistance to various anticancer agents, and displayed resistance to eribulin-induced effects on microtubule function and epithelial-mesenchymal transition (EMT).

DOI： 10.21873/anticanres.13559

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Objective: We evaluated the utility of continuous intraoperative neuromonitoring (CIONM) during surgery for thyroid cancer (TC) in an educational university hospital. Study Design: Prospective observational study. Methods: During the period April 2016 to March 2017, 43 patients who underwent standardized surgery with CIONM were prospectively included: 5 men and 38 women, 24-87 years old (median 52 years); 23 lobectomies and 20 total thyroidectomies with node dissection were conducted. Thirty-six operations were performed by a supervising surgeon, and seven were performed by trainees. Results: Temporal vocal cord paresis (VCP) was identified in 9 of 63 nerves at risk (14.3%) by postoperative laryngoscopy. VCP was not related to clinical factors including the surgeon's experience or the severe nerve stress demonstrated by CIONM. A significant relation only between VCP and loss of signal (LOS) was demonstrated (P = .002). The recovery of VCP was rapid (<1 month) in patients with global injury even when LOS was demonstrated, but was prolonged in patients demonstrating obvious segmental nerve injury and LOS. Conclusion: The present standard protocol of CIONM was useful to some extent to protect prolonged VCP, but not enough to detect every nerve stress causing VCP during TC surgery. On the other hand, CIONM is a promising method that could contribute surgical education at training hospitals enabling the instant confirmation of the procedure safely. Levels of Evidence: 3b.

DOI： 10.1002/lio2.290

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: A higher density of tumor-infiltrating lymphocytes (TILs) can lead to greater therapeutic effects and improved prognoses in cancer treatment. Similar results have been observed in breast cancer, particularly in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-enriched breast cancer. Calcium channel blockers (CCBs) are antihypertensive drugs (AHTs) that have also been reported to suppress the functions of T cells and macrophages. In this study, we evaluated TILs before pre-operative chemotherapy (POC) in breast cancer and retrospectively analyzed the correlation between CCBs and TILs or prognosis. METHODS: Of the patients treated with POC, 338 who had evaluable TILs were enrolled in this study. The correlations among TILs were evaluated according to standard methods, and CCB use and prognosis were investigated retrospectively. RESULTS: Before POC, 65 patients (19.2%) took AHTs (CCBs: 41/338, 12.1%). The TIL density was significantly lower among patients administered CCBs for the group of all patients and for patients with TNBC (p = 0.040, p = 0.009, respectively). Additionally, patients with TNBC who were administered CCBs showed significantly lower response rates for POC (p = 0.040). In all patients receiving POC, no significant differences in disease-free survival (DFS) or overall survival (OS) were observed in patients administered CCBs (p = 0.712, p = 0.478, log-rank tests, respectively). Furthermore, no significant differences were found, even in patients with TNBC (DFS: p = 0.441, OS: p = 0.727, log-rank tests, respectively). CONCLUSIONS: In patients with TNBC undergoing treatment for hypertension with CCBs, TILs in the needle biopsy specimens before treatment were significantly lower, and the response rate of POC was not sufficient. Thus, the immunosuppressive effects of CCBs may also affect the immune microenvironment.

DOI： 10.1186/s12885-019-5828-5

PubMed

DOI： 10.11477/mf.1411202114

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Several studies have established a positive relationship between quality of life (QOL) and prognosis in patients with various cancer types. This study investigated QOL of elderly patients with primary hormone receptor-positive breast cancer who chose endocrine therapy as their first-line treatment. PATIENTS AND METHODS: QOL-ACD-B scores were evaluated before and after endocrine therapy for 75 patients. The results of the interviews were used to determine the Charlson Comorbidity Index. RESULTS: In a univariate analysis, baseline objective response rate (p=0.009), and increase in QOL (p=0.037) significantly correlated with longer progression-free survival time. There was a correlation between 3-month QOL score and longer overall survival in the multivariate analysis (p=0.035). CONCLUSION: In elderly patients with breast cancer who underwent first-line endocrine therapy, improved QOL at 3 months after treatment initiation correlated with prolonged progression-free survival. High QOL scores were associated with prolonged overall survival.

DOI： 10.21873/anticanres.13424

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

DOI： 10.1007/s00280-019-03836-z

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVE: To investigate the effect of abatacept (ABA) on preventing joint destruction in biological disease-modifying anti-rheumatic drug (bDMARD)-naïve rheumatoid arthritis (RA) patients in real-world clinical practice. PATIENTS AND METHODS: RA patients were collected from the ABROAD (ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD) study cohort. They had moderate or high disease activity and were treated with ABA as a first-line bDMARD. Radiographic change between baseline and 1 year after ABA treatment was assessed with the van der Heijde's modified Total Sharp Score (mTSS). Predictive factors for structural remission (St-REM), defined as ΔmTSS ≤0.5/year, were determined. RESULTS: Among 118 patients, 81 (67.5%) achieved St-REM. Disease duration <3 years (odds ratio (OR) = 3.152, p = .007) and slower radiographic progression (shown as 'baseline mTSS/year <3', OR = 3.727, p = .004) were independently significant baseline predictive factors for St-REM irrespective of age and sex. St-REM prevalence increased significantly if clinical remission based on the Simplified Disease Activity Index was achieved at least once until 24 weeks after ABA treatment. CONCLUSION: Shorter disease duration, smaller radiographic progression at baseline, and rapid clinical response were predictive factors for sustained St-REM after ABA therapy in bDMARD-naïve RA patients.

DOI： 10.1080/14397595.2018.1482609

PubMed

Publishing type：Research paper (scientific journal)  

ソナゾイド造影超音波検査(contrast-enhanced ultrasonography:CEUS)は腫瘤内の微細血流を検出でき、乳房腫瘤性病変の良悪性の鑑別、術前治療の効果判定、病変の広がり診断に有用である。しかしこれらは乳癌全般に関する報告であり、特殊型乳癌である粘液癌におけるCEUSの有用性の報告は少なく、一定の見解が得られていない。今回、乳腺粘液癌4例に対してCEUSを施行し、病理組織所見と超音波像を比較検討したので報告する。2014年10月から2016年12月に当院でCEUSを施行し、針生検あるいは切除標本にて粘液癌と診断された4例を対象とした。診断装置はGE Healthcare社製LOGIQ E9、プローブはML6-15-Dを使用し、ソナゾイド(0.015ml/kg)を注入後、約1分間断面を固定して観察した後、病変全体のスイープスキャンを行った。病理にて純型粘液癌と診断された1例はCEUSにて明らかな染影を認めなかった。一方、混合型粘液癌と診断された3例では不均一な染影を認めた。純型粘液癌と混合型粘液癌で染影所見に相違がみられた。混合型においては、粘液に腫瘍細胞が浮遊する純型の部分と間質に腫瘍細胞が浸潤する部分の混在の様子を反映して、CEUSにおいて不均一で多彩な染影所見を呈したものと考えられた。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Disseminated intravascular coagulation (DIC) that occurs during cancer therapy prevents continuation of therapy, contributing to a worse prognosis. While recombinant human-soluble thrombomodulin (rhTM), a new DIC drug, has occasionally shown its efficacy in DIC associated with infection and blood cancer, its efficacy in patients with solid tumors has been unproven. This review presents the results on the efficacy and safety of rhTM as a DIC drug in patients with solid tumors that have been confirmed by the clinical data of three previous reports. The number of cases in each study was 101, 123 and 40. The respective DIC resolution rate was 34.0%, 35.2% and 32.5%, and the 28-day survival rate was 55.4%, 52.0% and 40.0%. Although comparison with other anti-DIC therapies is required, rhTM therapy is considered one of the treatment options of DIC in patients with solid tumors.

DOI： 10.21873/anticanres.13342

PubMed

Publishing type：Research paper (scientific journal)  

ソナゾイド造影超音波検査(contrast-enhanced ultrasonography:CEUS)は腫瘤内の微細血流を検出でき、乳房腫瘤性病変の良悪性の鑑別、術前治療の効果判定、病変の広がり診断に有用である。しかしこれらは乳癌全般に関する報告であり、特殊型乳癌である粘液癌におけるCEUSの有用性の報告は少なく、一定の見解が得られていない。今回、乳腺粘液癌4例に対してCEUSを施行し、病理組織所見と超音波像を比較検討したので報告する。2014年10月から2016年12月に当院でCEUSを施行し、針生検あるいは切除標本にて粘液癌と診断された4例を対象とした。診断装置はGE Healthcare社製LOGIQ E9、プローブはML6-15-Dを使用し、ソナゾイド(0.015ml/kg)を注入後、約1分間断面を固定して観察した後、病変全体のスイープスキャンを行った。病理にて純型粘液癌と診断された1例はCEUSにて明らかな染影を認めなかった。一方、混合型粘液癌と診断された3例では不均一な染影を認めた。純型粘液癌と混合型粘液癌で染影所見に相違が

Publishing type：Research paper (scientific journal)  

DOI： 10.21873/anticanres.13316

PubMed

J-GLOBAL

DOI： 10.34449/j0096.05.01_0034-0037

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12893-019-0494-8

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.3892/mco.2018.1778

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1002/bjs5.50108

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: The immune tumor microenvironment (iTME) is thought to affect the response to chemotherapy, and tumor-infiltrating lymphocytes (TILs) are often used as an indicator to evaluate the iTME. Smoking is involved in carcinogenesis, the relationship between smoking and the iTME of lung cancer has been reported. We hypothesized that smoking would affect the iTME of breast cancer and aimed to examine this relationship based on the amount of pre-diagnosis smoking and the subsequent effects on treatment response and prognosis. METHODS: This retrospective study evaluated data from 149 patients who underwent preoperative chemotherapy for triple-negative or HER2-enriched breast cancer. TILs were assessed in biopsy specimens at diagnosis. The data of all patients were used to calculate each patient's smoking amount based on pack-years. RESULTS: Relative to the low smoking group, the high smoking group had a significant greater TILs density (p = 0.043) and a significantly better pathological complete response (pCR) rate (p = 0.042). However, there was no significant difference according to smoking amount in disease-free survival (p = 0.114) or overall survival (p = 0.347). CONCLUSIONS: Smoking may influence the iTME, with an activated iTME being associated with pCR rate. Therefore, controlled activation of the microenvironment in this setting may help improve patients' prognosis.

DOI： 10.1186/s12967-019-1773-y

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000501766

PubMed

Publishing type：Research paper (scientific journal)  

It has been reported that contrast-enhanced ultrasonography (CEUS) can detect minute blood flows in breast tumors. As such, CEUS is a useful modality for diagnosing breast tumors. Although there are some CEUS studies of breast cancer in the literature, there are few reports of mucinous carcinoma of the breast. Between October 2014 and December 2016, we retrospectively enrolled four mucinous breast cancer patients who underwent CEUS examinations in this study. We used a LOGIQ E9 (GE Healthcare) with a ML6-15-D linear transducer. We acquired CEUS images for about 1 minute after intravenous injection of Sonazoid (0.015 ml/kg). Pathological findings in three cases revealed mixed types of mucinous carcinoma, and one case had a pure type. The mixed-type mucinous carcinomas showed ring-like enhancement or heterogeneous enhancement. And the pure-type mucinous carcinoma exhibited no apparent enhancement. The results in this study implied that CEUS findings of mixed-type mucinous carcinomas were different from those of pure-type ones. We conjectured that the contrast-enhanced appearance of mucinous breast carcinomas was dependent on the volume of invasive components.

DOI： 10.3179/jjmu.JJMU.A.134

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

PURPOSE: The purpose of this study was to compare the efficacy of the pre-prescription of garenoxacin mesylate hydrate (GRNX) with that of moxifloxacin hydrochloride (MFLX) in the management of breast cancer patients with low-risk febrile neutropenia. METHODS: Data from female patients who had been instructed to take previously prescribed oral GRNX or MFLX for 3 days during adjuvant and neoadjuvant chemotherapy if their body temperature exceeded 38 °C were analyzed. This study compared the effectiveness between these fluoroquinolones using a propensity score matching analysis. RESULTS: The 330 patients received 1192 administrations of chemotherapy between May 2007 and April 2014 and 136 (41.2%) patients had a total of 212 (17.8%) febrile episodes. The frequencies of febrile episodes were 19.5% (113/579) and 16.2% (99/613) in the GRNX and MFLX groups, respectively. After propensity score matching, 384 episodes were matched in each group. Febrile events occurred in 80 and 56 cases in the GRNX and MFLX groups, respectively. Treatment success was identified in 80.0% (64/80) of cases in the GRNX group and 64.3% (36/56) of cases in the MFLX group (P = 0.0494). Additionally, the therapeutic use of granulocyte-colony stimulating factor was 6.3% (5/80) of cases in the GRNX group and 17.9% (10/56) of cases in the MFLX group (P = 0.0498). There were few differences in the frequency of adverse effects between the two groups. CONCLUSIONS: These results indicate that the pre-prescription of GRNX may be a more effective option for the management of low-risk febrile neutropenia during adjuvant and neoadjuvant chemotherapy for breast cancer.

DOI： 10.1007/s00520-018-4589-z

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 72-year-old woman visited our hospital with the chief complaint of a mass in the right breast. Breast ultrasonography revealed a hypoechoic area with a distinct border in the right breast. A core needle biopsy showed the proliferation of spindle cells in the stroma, and she was diagnosed with stromal sarcoma or malignant phyllodes tumor. Right lumpectomy was performed. Pathological examination revealed a malignant phyllodes tumor with a sarcomatous lesion. Although she did not receive adjuvant chemotherapy, she is alive without any recurrence 2 years after the surgery. It is difficult to distinguish phyllodes tumors from stromal sarcoma, based on core needle biopsy, and the prognosis of malignant phyllodes tumors with distant metastases is poor. Rapid surgery to determine an accurate diagnosis and careful follow-up after surgery are impor- tant.

PubMed

J-GLOBAL

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

症例は72歳、女性。右乳房腫瘤を自覚し近医を受診した。精査加療目的に当院紹介となった。画像検査で右乳腺に比較的境界明瞭な腫瘤を認めた。針生検では間質に多形性の核を伴う紡錘形細胞が増殖しており、間質肉腫または悪性葉状腫瘍が疑われたため、確定診断を目的に乳腺腫瘤切除術を施行した。摘出標本の病理組織学的検査では、ほとんどが非上皮性の肉腫様であったが、一部に既存の乳管上皮を認めたため悪性葉状腫瘍の診断に至った。術後補助療法は施行せず術後2年間、無再発生存中である。針生検で葉状腫瘍と間質肉腫の鑑別を行うことは困難なこともあり、また遠隔転移例での予後は不良であることから、早期に摘出生検による確定診断を付けるとともに術後の厳重な経過観察が必要と考えられる。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は72歳、女性。右乳房腫瘤を自覚し近医を受診した。精査加療目的に当院紹介となった。画像検査で右乳腺に比較的境界明瞭な腫瘤を認めた。針生検では間質に多形性の核を伴う紡錘形細胞が増殖しており、間質肉腫または悪性葉状腫瘍が疑われたため、確定診断を目的に乳腺腫瘤切除術を施行した。摘出標本の病理組織学的検査では、ほとんどが非上皮性の肉腫様であったが、一部に既存の乳管上皮を認めたため悪性葉状腫瘍の診断に至った。術後補助療法は施行せず術後2年間、無再発生存中である。針生検で葉状腫瘍と間質肉腫の鑑別を行うことは困難なこともあり、また遠隔転移例での予後は不良であることから、早期に摘出生検による確定診断を付けるとともに術後の厳重な経過観察が必要と考えられる。(著者抄録)

Publishing type：Research paper (scientific journal)  

遺伝性乳癌卵巣癌症候群(HBOC)では、男性乳癌や膵癌の既往が重要となり、BRCA遺伝子変異を考慮して診断を進めるべきである。また、進行膵癌は多様な転移を来し、まれではあるが乳腺組織への転移の報告も散見される。今回われわれは、膵癌乳腺転移との鑑別を要した膵癌・男性乳癌重複の1例を経験したので報告する。症例は67歳、男性。発熱、右季肋部痛、全身倦怠感を主訴に近医を受診し、CT精査にて膵尾部癌多発肝転移・腹膜転移が疑われ、当院紹介となった。家族歴に特記すべき事項はなかった。左前胸部に約2cm大の弾性硬の腫瘤を認め、超音波検査で左乳腺C領域に2.8cm大の内部不均質で境界不明瞭な腫瘤が確認された。膵癌からの乳腺転移も否定し得ず、針生検を行ったところ、病理所見より乳腺原発が明らかとなった。以上より、膵尾部癌、cT4N1M1、Stage IVおよび原発性乳癌、cT2N0M0、Stage IIAとの同時性重複癌とした。全身精査中に腫瘍増大により肝不全が進行、best supportive care(BS

Publishing type：Research paper (scientific journal)  

症例は61歳、女性。検診マンモグラフィにて左乳腺腫瘤を指摘され、当院受診となった。超音波検査にて左乳腺BD領域に15.5×7.2mm大の不整形腫瘤を認め、吸引式乳腺組織生検(vacuum-assisted biopsy:VAB)を行うも、悪性所見は認められなかった。しかしながら3ヵ月後、腫瘤は24.2×16.5mm大に増大し、腋窩にも転移が疑われる複数個のリンパ節腫大が認められた。乳腺腫瘤に対し再度VABを行うものの悪性所見は認めず、腋窩リンパ節に対する針生検(core needle biopsy:CNB)より乳癌の診断に至った。手術は単純乳房切除術および腋窩リンパ節郭清を施行、摘出標本の乳腺組織より梗塞壊死を伴う充実腺管癌との確定診断が得られた。腋窩リンパ節転移は合計23個に確認された。今回われわれは、急速に増大する梗塞壊死を伴う乳癌を経験したので、若干の文献的考察を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

アポクリン腺癌は比較的まれな皮膚原発の悪性腫瘍であり、腋窩に好発するとされている。転移性腺癌、副乳癌や乳腺原発アポクリン癌などが鑑別として重要になるが、診断が困難な症例も存在する。症例は86歳、女性。右腋窩の胸壁腫瘤の精査加療目的にて当院に紹介となった。理学所見では、右腋窩に皮膚潰瘍を伴った約4cm大の腫瘤を認めた。超音波検査では、右腋窩に約4cm大の腫瘤、また転移を疑わせるリンパ節腫大が複数個確認された。CTにて遠隔転移は認めなかった。原発巣の精査目的にて吸引式乳腺組織生検を施行し、アポクリン癌(ER強陽性、PgR陰性、HER2-FISH陰性、Ki-67 13.6%)の病理組織学的診断を得た。ER陽性のため、術前診断は右乳腺アポクリン癌、cT4N1M0、Stage IIIbとし、単純乳房切除および腋窩リンパ節郭清術を施行した。病理組織学的診断では腫大した類円形核を有する異形細胞が確認され、乳腺原発アポクリン癌、pT4N2M0、Stage IIIb(45×25mm、tf2、na2、mc1、ly1、v2、ER強陽性、P

Publishing type：Research paper (scientific journal)  

乳房Paget病は、乳癌が乳管を経て乳頭および乳輪の表皮内に進展したもので乳癌の一表現型と考えられている。通常の浸潤性乳管癌との重複はまれとされているが、組織起源については議論の分かれるところである。症例は50歳、女性。検診マンモグラフィにて異常石灰化を指摘され、当院紹介となった。超音波検査では、左乳腺A領域に2.4×1.3×1.6cm大の辺縁不整・境界不明瞭な低エコー腫瘤が確認され、針生検での病理診断にて非浸潤性乳管癌と診断された。転移を疑う術前所見はなく、左非浸潤性乳管癌、cTisN0M0、Stage 0との診断下に単純乳房切除術およびセンチネルリンパ節生検を施行した。術中、リンパ節に転移が認められたために腋窩リンパ節郭清術を追加した。手術標本の病理診断では、主病巣に複数の部位で浸潤成分が認められた。さらに乳頭部の表皮内から豊かな細胞質を有した異型細胞の集塊が認められ、Paget病との診断を得た。最終診断は、Paget病を併存した浸潤性乳癌、pT1aN3M0、Stage IIIc、Luminal HER2とした。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は40歳、女性。右乳癌に対して乳腺部分切除術および腋窩郭清を施行した。最終診断は、T2N0M0、Stage IIA、mucinous、ly3、v0、ER弱陽性、PgR弱陽性であった。残存乳腺に放射線照射を行った後に術後補助療法を5年間行い、その後は無治療で経過観察していた。手術から7年後のCT検査で両側肺転移を認め、気管支鏡下生検ではER/PgR/HER2=強陽性/強陽性/弱陽性の診断であった。一次内分泌療法を行ったところ、約3年間の病状安定を得た。病状進行後に二次内分泌療法へ変更し、さらに3年間の奏効を獲得した。その後letrozole単剤療法に切り替え、さらに3年間腫瘍縮小を維持している。ホルモン受容体陽性乳癌の再発治療においては、再発までの期間や再生検によるホルモン受容体の発現状況の確認など内分泌療法の感受性を考慮した上で治療に当たることが重要である。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は73歳、女性。左乳房腫瘤を自覚し近医を受診し、精査加療目的に当院紹介となった。乳腺超音波検査にて、左EC領域に不整形の低エコー腫瘤を認めた。同部位の針生検による病理組織学的検査では充実性に増殖する腫瘍を認め、免疫組織染色にてE-cadherin陽性、シナプトフィジン陽性、クロモグラニンA陽性、CD56陰性であり、神経内分泌癌と考えられた。また、ER強陽性、PgR強陽性、HER2陰性であった。CT検査や骨シンチグラフィではリンパ節転移や遠隔転移を認めなかった。手術療法を優先し、単純乳房切除術およびセンチネルリンパ節生検を施行した。最終病理診断は神経内分泌癌(T2N0M0、Stage IIA、Luminal A-like)であった。術後は乳癌サブタイプを考慮し、内分泌療法を予定している。乳腺神経内分泌癌はまれである。他臓器からの乳腺転移の可能性を考慮し、画像精査を行うことが重要である。(著者抄録)

Publishing type：Research paper (scientific journal)  

DOI： 10.21873/anticanres.13041

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

遺伝性乳癌卵巣癌症候群(HBOC)では、男性乳癌や膵癌の既往が重要となり、BRCA遺伝子変異を考慮して診断を進めるべきである。また、進行膵癌は多様な転移を来し、まれではあるが乳腺組織への転移の報告も散見される。今回われわれは、膵癌乳腺転移との鑑別を要した膵癌・男性乳癌重複の1例を経験したので報告する。症例は67歳、男性。発熱、右季肋部痛、全身倦怠感を主訴に近医を受診し、CT精査にて膵尾部癌多発肝転移・腹膜転移が疑われ、当院紹介となった。家族歴に特記すべき事項はなかった。左前胸部に約2cm大の弾性硬の腫瘤を認め、超音波検査で左乳腺C領域に2.8cm大の内部不均質で境界不明瞭な腫瘤が確認された。膵癌からの乳腺転移も否定し得ず、針生検を行ったところ、病理所見より乳腺原発が明らかとなった。以上より、膵尾部癌、cT4N1M1、Stage IVおよび原発性乳癌、cT2N0M0、Stage IIAとの同時性重複癌とした。全身精査中に腫瘍増大により肝不全が進行、best supportive care(BSC)に至った。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は61歳、女性。検診マンモグラフィにて左乳腺腫瘤を指摘され、当院受診となった。超音波検査にて左乳腺BD領域に15.5×7.2mm大の不整形腫瘤を認め、吸引式乳腺組織生検(vacuum-assisted biopsy:VAB)を行うも、悪性所見は認められなかった。しかしながら3ヵ月後、腫瘤は24.2×16.5mm大に増大し、腋窩にも転移が疑われる複数個のリンパ節腫大が認められた。乳腺腫瘤に対し再度VABを行うものの悪性所見は認めず、腋窩リンパ節に対する針生検(core needle biopsy:CNB)より乳癌の診断に至った。手術は単純乳房切除術および腋窩リンパ節郭清を施行、摘出標本の乳腺組織より梗塞壊死を伴う充実腺管癌との確定診断が得られた。腋窩リンパ節転移は合計23個に確認された。今回われわれは、急速に増大する梗塞壊死を伴う乳癌を経験したので、若干の文献的考察を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

アポクリン腺癌は比較的まれな皮膚原発の悪性腫瘍であり、腋窩に好発するとされている。転移性腺癌、副乳癌や乳腺原発アポクリン癌などが鑑別として重要になるが、診断が困難な症例も存在する。症例は86歳、女性。右腋窩の胸壁腫瘤の精査加療目的にて当院に紹介となった。理学所見では、右腋窩に皮膚潰瘍を伴った約4cm大の腫瘤を認めた。超音波検査では、右腋窩に約4cm大の腫瘤、また転移を疑わせるリンパ節腫大が複数個確認された。CTにて遠隔転移は認めなかった。原発巣の精査目的にて吸引式乳腺組織生検を施行し、アポクリン癌(ER強陽性、PgR陰性、HER2-FISH陰性、Ki-67 13.6%)の病理組織学的診断を得た。ER陽性のため、術前診断は右乳腺アポクリン癌、cT4N1M0、Stage IIIbとし、単純乳房切除および腋窩リンパ節郭清術を施行した。病理組織学的診断では腫大した類円形核を有する異形細胞が確認され、乳腺原発アポクリン癌、pT4N2M0、Stage IIIb(45×25mm、tf2、na2、mc1、ly1、v2、ER強陽性、PgR陰性、HER2強陽性、Ki-67 6%)の診断を得た。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 40-year-old woman underwent right partial mastectomy and axillary lymph node dissection. Pathological examination confirmed right breast cancer(T2N0M0, Stage ⅡA, mucinous, ly3, v0, weakly positive ER and PgR). After surgery, she received radiotherapy for residual mammary gland cancer and endocrine therapy as adjuvant treatment for 5 years. Seven years after the first surgery, computed tomography showed multiple lung tumors. Transbronchial lung biopsy revealed lung metastasis from breast cancer(strongly positive ER and PgR, negative HER2). She received first-line endocrine therapy, and the response was classified as stable disease(SD). Three years later, the disease control became poor. Second-line endocrine therapy was then administered, and the response was classified as partial response(PR)for 3 years. After that, we modified the regimen to monotherapy of letrozole, and she achieved PR for a further 3 years. In the treatment for patients with metastatic hormone receptor-positive breast cancer, it is important to consider the sensitivity of endocrine therapy, such as relapse-free survival or the expression of hormone receptors in metastatic tumors.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

History of male breast cancer and pancreatic cancer are important for diagnosis of hereditary breast and ovarian cancer syndrome(HBOC), while advanced pancreatic cancer is reported to have metastasis to mammary gland tissue. A 67-year-old man visited a local hospital because fever and right hypochondrial pain. Computed tomography scan revealed pancreatic cancer with multiple liver metastasis and peritoneal metastasis. He was referred to our hospital for further evaluation and treatment. No particular family history of malignancy was formed. A palpable lump was found in his left breast. Ultrasonography revealed 2.8 cm sized mass that had heterogenous internal echo and rough border. The background mammary gland showed gynecomastia. Since it was difficult primary breast cancer with metastatic tumor originated from pancreas cancer a core needle biopsy was performed. The finding of pathological examination showed invasive carcinoma with hormonal receptor negative and HER2 negative feature. CK7 and CK19 were both positive. Although it was difficult to male differentiation whether the tumor was primary a metastatic, we diagnosed as synchronous duplicated cancer of pancreas and breast due to existence of gynecomastia. Since hepatic failure due to tumor growth advanced prior to treatment start, the treatment policy became best supportive care.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Paget's disease of the breast is usually localized in the nipple epidermis and lactiferous duct located near the nipple. Here, we report a rare case of synchronous breast carcinoma with Paget's disease and invasive ductal carcinoma. A 50-year-old woman was admitted to our hospital because of abnormalities in screening mammography findings. Ultrasonography(US) findings showed a 2.4×1.3×1.6 cm sized hypoechoic lesion in a region of the left mammary gland. Computed tomography (CT)findings did not reveal distant metastasis. Magnetic resonance imaging(MRI)revealed an approximately 2.2 cm sized irregular tumor. The pretreatment diagnosis was left non-invasive ductal carcinoma(cTisN0M0, Stage 0), and surgery was performed. The tumor was found in the range of 40.2×15.0 mm, many of which were breast ductal growth. An infiltrated image was confirmed at multiple sites, but the maximum size was 2.5×1.5 mm. Pathological findings of the main lesion revealed papillotubular carcinoma. Agglomeration of heterotypic cells with abundant cytoplasm was observed in the epidermis of the papilla. The final diagnosis was invasive breast cancer(pT1aN3M0, Stage Ⅲc, Luminal HER2)coexisting with Paget's disease.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 73-year-old woman visited our hospital with the chief complaint of a mass in the left breast. Breast ultrasonography revealed a hypoechoic area in the left breast. A core needle biopsy showed the proliferation of solid tumor cells. Immunohistochemistry indicated strongly positive expression of E-cadherin, synaptophysin, and chromogranin A. We then diagnosed her with breast neuroendocrine carcinoma. The expression of estrogen receptor(ER)and progesterone receptor(PgR)were also strongly positive, and the expression of human epidermal growth factor receptor 2(HER2)was negative. Computed tomography( CT)and bone scintigraphy revealed no metastasis. Simple mastectomy of the left breast and sentinel lymph node biopsy were performed. Final pathological examination of the tumor also led to the diagnosis of breast neuroendocrine carcinoma(T2N0M0, StageⅡA, Luminal A-like). After surgery, endocrine therapy is planned, considering the breast cancer subtype. Breast neuroendocrine carcinoma is rare. It is important to consider the possibility of metastasis from other organs to the breast.

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

症例は72歳、女性。右乳房腫瘤を自覚し近医を受診した。精査加療目的に当院紹介となった。画像検査で右乳腺に比較的境界明瞭な腫瘤を認めた。針生検では間質に多形性の核を伴う紡錘形細胞が増殖しており、間質肉腫または悪性葉状腫瘍が疑われたため、確定診断を目的に乳腺腫瘤切除術を施行した。摘出標本の病理組織学的検査では、ほとんどが非上皮性の肉腫様であったが、一部に既存の乳管上皮を認めたため悪性葉状腫瘍の診断に至った。術後補助療法は施行せず術後2年間、無再発生存中である。針生検で葉状腫瘍と間質肉腫の鑑別を行うことは困難なこともあり、また遠隔転移例での予後は不良であることから、早期に摘出生検による確定診断を付けるとともに術後の厳重な経過観察が必要と考えられる。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

遺伝性乳癌卵巣癌症候群(HBOC)では、男性乳癌や膵癌の既往が重要となり、BRCA遺伝子変異を考慮して診断を進めるべきである。また、進行膵癌は多様な転移を来し、まれではあるが乳腺組織への転移の報告も散見される。今回われわれは、膵癌乳腺転移との鑑別を要した膵癌・男性乳癌重複の1例を経験したので報告する。症例は67歳、男性。発熱、右季肋部痛、全身倦怠感を主訴に近医を受診し、CT精査にて膵尾部癌多発肝転移・腹膜転移が疑われ、当院紹介となった。家族歴に特記すべき事項はなかった。左前胸部に約2cm大の弾性硬の腫瘤を認め、超音波検査で左乳腺C領域に2.8cm大の内部不均質で境界不明瞭な腫瘤が確認された。膵癌からの乳腺転移も否定し得ず、針生検を行ったところ、病理所見より乳腺原発が明らかとなった。以上より、膵尾部癌、cT4N1M1、Stage IVおよび原発性乳癌、cT2N0M0、Stage IIAとの同時性重複癌とした。全身精査中に腫瘍増大により肝不全が進行、best supportive care(BS

症例は61歳、女性。検診マンモグラフィにて左乳腺腫瘤を指摘され、当院受診となった。超音波検査にて左乳腺BD領域に15.5×7.2mm大の不整形腫瘤を認め、吸引式乳腺組織生検(vacuum-assisted biopsy:VAB)を行うも、悪性所見は認められなかった。しかしながら3ヵ月後、腫瘤は24.2×16.5mm大に増大し、腋窩にも転移が疑われる複数個のリンパ節腫大が認められた。乳腺腫瘤に対し再度VABを行うものの悪性所見は認めず、腋窩リンパ節に対する針生検(core needle biopsy:CNB)より乳癌の診断に至った。手術は単純乳房切除術および腋窩リンパ節郭清を施行、摘出標本の乳腺組織より梗塞壊死を伴う充実腺管癌との確定診断が得られた。腋窩リンパ節転移は合計23個に確認された。今回われわれは、急速に増大する梗塞壊死を伴う乳癌を経験したので、若干の文献的考察を加えて報告する。(著者抄録)

アポクリン腺癌は比較的まれな皮膚原発の悪性腫瘍であり、腋窩に好発するとされている。転移性腺癌、副乳癌や乳腺原発アポクリン癌などが鑑別として重要になるが、診断が困難な症例も存在する。症例は86歳、女性。右腋窩の胸壁腫瘤の精査加療目的にて当院に紹介となった。理学所見では、右腋窩に皮膚潰瘍を伴った約4cm大の腫瘤を認めた。超音波検査では、右腋窩に約4cm大の腫瘤、また転移を疑わせるリンパ節腫大が複数個確認された。CTにて遠隔転移は認めなかった。原発巣の精査目的にて吸引式乳腺組織生検を施行し、アポクリン癌(ER強陽性、PgR陰性、HER2-FISH陰性、Ki-67 13.6%)の病理組織学的診断を得た。ER陽性のため、術前診断は右乳腺アポクリン癌、cT4N1M0、Stage IIIbとし、単純乳房切除および腋窩リンパ節郭清術を施行した。病理組織学的診断では腫大した類円形核を有する異形細胞が確認され、乳腺原発アポクリン癌、pT4N2M0、Stage IIIb(45×25mm、tf2、na2、mc1、ly1、v2、ER強陽性、P

Publishing type：Research paper (scientific journal)  

乳房Paget病は、乳癌が乳管を経て乳頭および乳輪の表皮内に進展したもので乳癌の一表現型と考えられている。通常の浸潤性乳管癌との重複はまれとされているが、組織起源については議論の分かれるところである。症例は50歳、女性。検診マンモグラフィにて異常石灰化を指摘され、当院紹介となった。超音波検査では、左乳腺A領域に2.4×1.3×1.6cm大の辺縁不整・境界不明瞭な低エコー腫瘤が確認され、針生検での病理診断にて非浸潤性乳管癌と診断された。転移を疑う術前所見はなく、左非浸潤性乳管癌、cTisN0M0、Stage 0との診断下に単純乳房切除術およびセンチネルリンパ節生検を施行した。術中、リンパ節に転移が認められたために腋窩リンパ節郭清術を追加した。手術標本の病理診断では、主病巣に複数の部位で浸潤成分が認められた。さらに乳頭部の表皮内から豊かな細胞質を有した異型細胞の集塊が認められ、Paget病との診断を得た。最終診断は、Paget病を併存した浸潤性乳癌、pT1

症例は40歳、女性。右乳癌に対して乳腺部分切除術および腋窩郭清を施行した。最終診断は、T2N0M0、Stage IIA、mucinous、ly3、v0、ER弱陽性、PgR弱陽性であった。残存乳腺に放射線照射を行った後に術後補助療法を5年間行い、その後は無治療で経過観察していた。手術から7年後のCT検査で両側肺転移を認め、気管支鏡下生検ではER/PgR/HER2=強陽性/強陽性/弱陽性の診断であった。一次内分泌療法を行ったところ、約3年間の病状安定を得た。病状進行後に二次内分泌療法へ変更し、さらに3年間の奏効を獲得した。その後letrozole単剤療法に切り替え、さらに3年間腫瘍縮小を維持している。ホルモン受容体陽性乳癌の再発治療においては、再発までの期間や再生検によるホルモン受容体の発現状況の確認など内分泌療法の感受性を考慮した上で治療に当たることが重要である。(著者抄録)

症例は73歳、女性。左乳房腫瘤を自覚し近医を受診し、精査加療目的に当院紹介となった。乳腺超音波検査にて、左EC領域に不整形の低エコー腫瘤を認めた。同部位の針生検による病理組織学的検査では充実性に増殖する腫瘍を認め、免疫組織染色にてE-cadherin陽性、シナプトフィジン陽性、クロモグラニンA陽性、CD56陰性であり、神経内分泌癌と考えられた。また、ER強陽性、PgR強陽性、HER2陰性であった。CT検査や骨シンチグラフィではリンパ節転移や遠隔転移を認めなかった。手術療法を優先し、単純乳房切除術およびセンチネルリンパ節生検を施行した。最終病理診断は神経内分泌癌(T2N0M0、Stage IIA、Luminal A-like)であった。術後は乳癌サブタイプを考慮し、内分泌療法を予定している。乳腺神経内分泌癌はまれである。他臓器からの乳腺転移の可能性を考慮し、画像精査を行うことが重要である。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: The diagnosis of metastasis by sentinel lymph node biopsy (SLNB) in early breast cancer surgery provides an accurate view of the state of metastases to the axillary lymph nodes, and it has now become the standard procedure. In the present study, whether omission of axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is possible by evaluation of tumor-infiltrating lymphocytes (TILs) before NAC in cases without metastasis on diagnostic imaging, but with metastasis on SLNB, was retrospectively investigated. METHODS: A total of 91 patients with resectable, early-stage breast cancer, diagnosed as cT1-2, N0, M0, underwent SLNB and were treated with NAC. A semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in biopsy specimens of primary tumors prior to treatment was conducted. RESULTS: In cases with a low number of TILs, estrogen receptor expression was significantly higher (p = 0.044), and human epidermal growth factor receptor 2 (HER2) expression was significantly lower than in other cases (p = 0.019). The number of TILs was significantly lower in cases in which the intrinsic subtype was hormone receptor-positive breast cancer (HRBC) (p = 0.044). Metastasis to axillary lymph nodes was significantly more common in HER2-negative cases and cases with a low number of TILs (p = 0.019, p = 0.005, respectively). CONCLUSIONS: Even if macrometastases are found on SLNB in cN0 patients, it appears that ALND could be avoided after NAC in cases with a good immune tumor microenvironment of the primary tumor.

DOI： 10.1186/s12967-018-1692-3

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: The lymphocyte-to-monocyte ratio (LMR) has been used as a parameter reflecting systemic inflammation in several tumors, and is reportedly associated with prognosis in cancer patients. In this study, we evaluated the predictive value of LMR for progression and chemosensitivity in breast cancer patients treated with preoperative chemotherapy. METHODS: LMR was evaluated in 239 patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel with or without trastuzumab, and subsequent curative surgery. The correlations between LMR and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were evaluated retrospectively. We also evaluated the predictive value of neutrophil-to-lymphocyte ratio (NLR), and compared the predictive values of LMR and NLR. RESULTS: We set 6.00 as the cut-off level for LMR based on the receiver operating characteristic (ROC) curve. A total of 119 patients (49.8%) were classified in the high-LMR group and 120 (50.2%) were classified in the low-LMR group. The low-LMR group had significantly worse disease-free survival rate (DFS) in all patients (p = 0.005) and in triple-negative breast cancer patients (p = 0.006). However, there was no significant correlation between LMR and pCR. Multivariate analysis showed that low LMR was an independent risk factor for DFS (p = 0.008, hazard ratio = 2.245). However, there was no significant difference in DFS (p = 0.143, log-rank) between patients in the low- and high-NLR groups. CONCLUSIONS: LMR may be a useful prognostic marker in patients with breast cancer.

DOI： 10.1186/s12885-018-5051-9

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: The prognosis of breast cancer and the treatment response to neoadjuvant chemotherapy (NAC) differ depending on the intrinsic molecular subtypes. We evaluated the prognostic significance of immunohistological subtypes in patients with recurrent breast cancer after treatment with NAC and surgery. METHODS: A total of 237 patients with breast cancer treated with NAC and subsequent curative surgery between 2007 and 2015 were analyzed. The correlation between intrinsic molecular subtypes and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were investigated retrospectively. RESULTS: There were 55 (23.2%) patients with recurrence after surgery. No significant difference in post-recurrence survival (PRS) was noted among the subtypes (p = 0.397). In patients with estrogen receptor-positive human epidermal growth factor receptor (HER) 2-negative (luminal) malignancy, PRS was significantly better in the pCR group than in the non-pCR group (p = 0.031). Conversely, pCR was not a significant predictor of improved PRS in patients with triple-negative breast cancer (TNBC; p = 0.329). Multivariate analysis revealed that the efficacy of NAC [hazard ratio (HR) 300.204, p < 0.001] and the initial metastasis site (HR 15.037, p = 0.005) were independent predictors for PRS in patients with luminal breast cancer, while Ki-67 (HR 51.171, p = 0.020) and the initial metastasis site (HR 13.318, p = 0.048) were independent predictors for PRS in patients with TNBC. CONCLUSIONS: The prognostic factors for each intrinsic subtype should be evaluated separately in patients with recurrent breast cancer following NAC and surgery.

DOI： 10.1186/s12967-018-1679-0

PubMed

J-GLOBAL

Publishing type：Research paper (scientific journal)  

Purpose: Quality-of-life (QOL) has been reported to affect the prognosis of many types of cancer, and several studies used various QOL assessment tools to determine the relationship between QOL and cancer prognosis. In this study, QOL-Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-the Breast (QOL-ACD-B) was modified to be suitable for preoperative chemotherapy (POC) and was named the QOL-ACD-BP. Methods: A total of 300 patients were treated with POC after being diagnosed with breast cancer between February 2007 and December 2016 at our institute. We evaluated novel evaluation scale for QOL (QOL-ACD-BP) before and after POC in a retrospective manner. Results: In the multivariate analysis with overall survival, the high QOL before [p = 0.048, hazard ratio (HR) 0.441] or after POC (p = 0.030, HR 0.273) was an independent factor. Conclusion: Our study shows that QOL after POC may also affect prognosis and supported the importance of maintaining QOL in cancer treatment. In patients with breast cancer treated with POC, QOL-ACD-BP, which is a new QOL evaluation index, was found to be a useful tool for predicting the patients’ prognosis.

DOI： 10.1007/s00432-018-2670-0

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Background: Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune tumour microenvironment (iTME) and predict treatment response and outcome in breast cancer. We evaluated the prognostic significance of the levels of CD8+ TILs and forkhead box protein (FOXP3)-positive TILs before and after neoadjuvant chemotherapy (NAC). Patients and methods: We examined 136 patients with breast cancer treated with NAC. The number of CD8+ TILs and FOXP3+ TILs in biopsy specimens and residual tumours was evaluated by immunohistochemistry. Results: Patients with a high rate of change in the CD8/FOXP3 ratio (CFR) had significantly better recurrence-free survival (RFS) (p<0.001, log-rank). In multivariate analysis, the rates of change in the CD8+ TIL levels and the CFR were independent predictors for RFS (HR=2.304, p=0.036 and HR=4.663, p<0.001). In patients with triple-negative and hormone receptor-positive breast cancer, the rate of change in the CFR was an independent predictor for RFS (HR=13.021, p=0.002 and HR=4.377, p=0.003). Conclusion: Improvement in the iTME following NAC is correlated with good outcome. The rate of change in the CFR may be a useful biomarker to predict prognosis of patients treated with NAC.

DOI： 10.1136/esmoopen-2017-000305

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Immune responses in a tumour microenvironment can be evaluated by analysing tumour-infiltrating lymphocyte (TIL) density; this has been verified in the clinical setting. Although there are many reports on TIL density in primary tumours, little is known about its density in recurrent tumours. METHODS: Of 300 patients treated with neoadjuvant chemotherapy during the study period, 29 were considered for evaluation of TIL density in primary and recurrent tumours. We performed a retrospective analysis of the association between TIL density and prognosis. RESULTS: TIL density was significantly lower in recurrent tumours than in primary tumours (P = 0.007). There was no correlation between post-recurrence survival and TIL density in core-needle biopsy specimens obtained from primary tumours (P = 0.837). However, patients with high TIL density in recurrent tumours had significantly better post-recurrence survival than did the corresponding group with low TIL density (P = 0.041). Multivariate analysis revealed that high TIL density contributed significantly towards improving post-recurrence survival in all patients (P = 0.035; hazard ratio, 0.167). CONCLUSIONS: In recurrent breast cancer, a decrease in TILs density was observed as compared to the primary tumour, and this affects the poor prognosis after relapse.

DOI： 10.1038/s41416-018-0197-4

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.AM2018-5212

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.AM2018-3119

Publishing type：Research paper (scientific journal)  

Background/Aim: Several proteins involved in immune regulation and the relationship among these, the tumor microenvironment, and clinical outcomes of eribulin treatment were evaluated in advanced or metastatic breast cancer patients. Patients and Methods: This retrospective cohort study comprised 52 eribulin-treated locally advanced or metastatic breast cancer patients. Cancer tissue samples were obtained before and after treatment in 10 patients. Immunohistochemistry was performed to determine programmed death (PD)-1, CD8, and forkhead box P3 (FOXP3) expression by stromal tumor-infiltrating lymphocytes, and PD-ligand (L1) and PD-L2 expression by cancer cells. Results: Of the 10 patients, 5 were responders (partial response) and 5 were non-responders (stable disease, 2
progressive disease, 3) to eribulin. PD-1, PD-L2, and FOXP3 expression became negative in 5 patients, PD-L1 expression became negative in 6 patients, and CD8 expression became positive in 3 patients after treatment. The response to eribulin was significantly associated with PD-L1 and FOXP3 negative conversion (p=0.024 and 0.004, respectively). The change in E-cadherin expression (positive or negative) was also correlated with the changes in PD-L1 and FOXP3 (p=0.024 and 0.004, respectively). Kaplan–Meier analysis with log-rank tests revealed that progression-free survival and time-to-treatment failure were significantly longer in patients with PD-L1 and FOXP3 negative conversion (p=0.012 and 0.001
p=0.049 and 0.018, respectively). Conclusion: The efficacy of eribulin may be attributed to its biological effects on the immune system (reduction of PD-L1 and FOXP3 expression) through epithelial–mesenchymal transition suppression, and vascular remodeling and improvement of the tumor microenvironment.

DOI： 10.21873/anticanres.12541

PubMed

J-GLOBAL

Publishing type：Research paper (scientific journal)  

Purpose Numerous reports indicate that tumor-infiltrating lymphocytes (TILs) are a prognostic factor in various cancers and that they must be good biomarkers. However, the methods of evaluating TILs differ in each study
thus, there is not yet a standardized methodology for evaluating TILs. The purpose of this study is to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with colorectal cancer (CRC) using the new method proposed by the International TILs Working Group in breast cancer and to standardize the method of evaluating TILs in CRC. Methods We retrospectively reviewed a database of 160 patients with Stage II or III CRC. The density of TILs was assessed by measuring the area occupied by mononuclear cells over the stromal area on hematoxylin and eosin (H-E)-stained sections. We set 42% as the cut-off percentage of the area occupied by TILs according to the receiver operating characteristic curve, and we classified patients into the high-TILs and the low-TILs groups. Results The rates of relapse-free survival (RFS) and overall survival (OS) in the high-TILs group were significantly higher than those in the low-TILs group. A multivariate analysis showed that the density of TILs was independently associated with RFS and OS. Moreover, the density of TILs assessed by an observer was significantly associated with the density of TILs assessed by the automated imaging software program. Conclusions The new method for evaluating TILs, which was recommended by the International TILs Working Group in breast cancer, might be a useful predictive factor in colorectal cancer patients.

DOI： 10.1371/journal.pone.0192744

PubMed

Publishing type：Research paper (scientific journal)  

Background: "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. Methods: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. Results: There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p &lt
0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p &lt
0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479). Conclusions: PD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC.

DOI： 10.1186/s12967-018-1458-y

PubMed

Publishing type：Research paper (scientific journal)  

Background: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators. Methods: The subjects consisted of 30 patients who received the TPD regimen. The expression levels of estrogen receptor, progesterone receptor, Ki67, CD8, forkhead box protein (FOXP) 3, programmed death (PD) 1, programmed death ligand (PD-L) 1, CD163, phosphatase and tensin homolog and lymphocyte activation gene 3 were evaluated in biopsy specimens, by immunostaining. Results: CD8+, CD8/FOXP3 ratio (CFR)high and PD-L1- group had significantly longer PFS than the CD8-, CFRlow and PDL1+ group (p = 0.045, log-rank) (p = 0.007, log-rank) (p = 0.040, log-rank), respectively. The CFRhigh group had significantly better OS than the CFRlow group (p = 0.034, log-rank). In the univariate analysis, CD8+, CFRhigh groups extended PFS significantly (p = 0.027, hazard ratio [HR] = 0.162) (p = 0.008, HR = 0.195), respectively. The receiver operating characteristic (ROC) analyses showed that the results for CFR [area under the curve (AUC): 0.708] were better than those for other factors (AUC: CD8 = 0.681, FOXP3 = 0.639, PD1 = 0.528, PD-L1 = 0.681). Conclusions: This study shows with the TPD regimen, a high CFR leads to a high ORR and long PFS in HER2-positive breast cancer. CFR, therefore, may be one of the important prognostic factors for this disease.

DOI： 10.1186/s12967-018-1460-4

PubMed

Publishing type：Research paper (scientific journal)  

Background: The anticancer immune response has been reported to correlate with cancer progression. Tumor-infiltrating lymphocytes (TILs), which are one of the indicators of host immunity, affect the tumor growth, metastasis and chemoresistance. Both TILs in the primary tumor and those in the metastatic tumor have been reported to be a useful predictor of the survival and therapeutic outcome. However, the correlation between the density of TILs in the primary and metastatic tumor is unclear. The aim of this study was to elucidate the correlation between the density of TILs in the primary and metastatic tumor. Methods: A total of 24 patients with stage IV colorectal cancer who underwent concurrent resection of the primary tumor and liver metastasis were enrolled in order to assess the correlation between the density of TILs in the primary tumor and that in the metastatic tumor. Hematoxylin and eosin (HE)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by the measurement of the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. In addition, to evaluate TIL subsets and the activation/suppression status of the lymphocytes, immunohistochemistry for CD4, CD8, Forkhead boxprotein P3 (FOXP3), programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), inducible T-cell co-stimulator (ICOS), Glucocorticoid induced tumor necrosis factor receptor related protein (GITR), Human Leukocyte Antigen - antigen D Related (HLA-DR) and Granzyme B was performed, and the number of immunoreactive lymphocytes was counted. Results: According to the evaluation using the HE-stained sections, the density of tumor-infiltrating mononuclear inflammatory cells in the primary tumor was significantly associated with that in the metastatic tumor. In addition, according to the immunohistochemistry evaluation, the density of CD4+, CD8+ and FOXP3+ TILs in the primary tumor and that in the metastatic tumor were significantly correlated with that in the metastatic tumor. Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B and the PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor. Conclusions: The local immune status of the primary tumor was revealed to be similar to that of the metastatic tumor. This suggests that the evaluation of the local immunity of the primary tumor may be a substitute for the evaluation of the local immunity of the metastatic lesion. Therefore, information on the primary tumor may be useful when considering treatment strategies for metastatic lesions.

DOI： 10.1186/s12885-018-4276-y

PubMed

Publishing type：Research paper (scientific journal)  

Background: Chemotherapy with trastuzumab, pertuzumab and docetaxel (TPD regimen) is now strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER)2positive breast cancer. In this study, we analyzed the expression of HER 1–4 proteins, and investigated whether or not their expression was predictive of the response of advanced HER2-positive breast cancer to chemotherapy with the TPD regimen. Patients and Methods: The study consisted of 29 cases in which TPD regimen chemotherapy was carried out from September 2013 to November 2015. The expression levels of estrogen receptor (ER), progesterone receptor (PgR), Ki67, HER1, HER2, HER3 and HER4 were evaluated using immunostaining employing needle biopsy specimens. Results: The overall response rate (ORR) was significantly higher in the HER3-positive group than in the HER3-negative group (p=0.002). In prognostic analysis, the HER3-positive group showed a significant progression-free survival extension over the HER3-negative group (p=0.042, log-rank). In univariate analysis, objective response (p=0.004, hazard ratio(HR)=0.123) and positive HER3 expression (p=0.023, HR=0.279) significantly contributed to extension of progression-free survival interval. Conclusion: HER3 expression may be a useful factor for predicting the response of HER2-positive breast cancer to chemotherapy with the TPD regimen.

DOI： 10.21873/anticanres.12473

PubMed

Publishing type：Research paper (scientific journal)  

Background/Aim: Recent interest has focused on the significance of tumor-infiltrating lymphocytes (TILs) on the efficacies and outcomes of the treatment in breast cancer (BC). Based on the recent international recommendation to standardize the evaluation method, the clinical validity and utility of TILs in patients who underwent neoadjuvant chemotherapy (NAC) were investigated in the present study. Patients and Methods: TILs were evaluated in 177 patients with BC treated with NAC and subsequent curative surgery. The correlation between TILs evaluated according to the standard method and prognosis, including the efficacy of NAC, was investigated retrospectively. Results: In the high-TIL group (n=96) compared to the low-TIL group (n=81), triple-negative breast cancer (TNBC) (p&lt
0.001) and human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p=0.040) were significantly more frequent, and the pathological complete response (pCR) rate was significantly higher (p=0.003). Among patients with TNBC and those with HER2BC, the pCR rate was significantly higher in the high-TIL group than in the low-TIL group (p=0.013 and p=0.014, respectively). Multivariable analysis also showed that high-TIL status was an independent factor predicting favorable prognosis (hazard ratio(HR)=0.24, p=0.023 and HR=0.13, p=0.036). Biopsy specimens from local recurrence after successful NAC frequently showed TILs decreased. Conclusion: TILs may be a biomarker for predicting treatment response to NAC in patients with TNBC and HER2BC. A decrease in TILs may also be associated with tumor recurrence.

DOI： 10.21873/anticanres.12476

PubMed

Publishing type：Research paper (scientific journal)  

Background: Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the determination of treatment strategies since both PPL and PNM are classified as progressive disease based on the response evaluation criteria in solid tumors (RECIST) diagnostic criteria. On the other hand, tumor infiltrating lymphocytes (TILs) are effective when used as indicators for monitoring the immune tumor microenvironment (iTME) in the cancer host, and TILs play an important role as biomarkers in predicting prognosis and therapeutic effects. This study focused on the progression types of cancer in patients undergoing eribulin chemotherapy. In addition, the iTME in individuals with PPL and PNM was evaluated using TILs as a marker. Methods: Of the 52 patients with locally advanced or metastatic breast cancer who underwent chemotherapy with eribulin, 40 remained in the study, and 12 patients were dropout cases. The antitumor effect was evaluated based on the RECIST criteria using version 1.1. TILs were defined as the infiltrating lymphocytes within tumor stroma and were expressed in proportion to the field investigated. In PPL cases, the high-TIL group was considered as type I and the low-TIL group was classified as type II. In PNM cases, the high-TIL group was considered as type III and the low-TIL group was classified as type IV. Results: In 19 cases, individuals with type I progression had significantly longer progression free survival and overall survival (OS) compared to those with type III progression (p = 0.040, p &lt
0.001, log-rank). Individuals with type I progression had significantly prolonged survival post progression compared to those with type II progression (p = 0.048, log-rank). A multivariate analysis that validate the effect of OS showed that these were independent factors of good prognosis (p = 0.003
hazard ratio [HR] = 0.065) (p = 0.006
HR = 0.105). Conclusions: The effects of eribulin chemotherapy suggested that patients with progressive-type breast cancer that proliferates in a good iTME may have a good prognosis.

DOI： 10.1186/s12967-018-1443-5

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s40364-018-0124-0

Publishing type：Research paper (scientific journal)  

血友病を合併したBasedow病の症例は非常に稀である。今回われわれは甲状腺全摘出術を施行した1例を経験したので報告する。症例は25歳男性。内服コンプライアンスが不良であり、本人が手術を希望したため当院に紹介された。血友病に対しては、遺伝子組換え型血液凝固第VIII因子製剤を生下時より定期注射しており、凝固因子活性検査第VIII因子は1%未満で重症と判定されたが、日常生活には支障なかった。インヒビターのない血友病患者に対する止血治療ガイドライン2013に沿って、周術期の凝固因子製剤を投与した。凝固因子製剤のボーラス輸注では目標トラフ因子レベルを下回る時間帯が存在するため、持続静注を併用することとした。手術中も持続投与は継続した。手術中は止血に難渋することなく終了した。術後経過良好であり、術後再出血は認めなかった。血友病を合併したBasedow病に手術療法を選択した例は本邦では報告がなく症例の蓄積と検討が必要と考えられる。(著者抄録)

Publishing type：Research paper (scientific journal)  

血友病を合併したBasedow病の症例は非常に稀である。今回われわれは甲状腺全摘出術を施行した1例を経験したので報告する。症例は25歳男性。内服コンプライアンスが不良であり、本人が手術を希望したため当院に紹介された。血友病に対しては、遺伝子組換え型血液凝固第VIII因子製剤を生下時より定期注射しており、凝固因子活性検査第VIII因子は1%未満で重症と判定されたが、日常生活には支障なかった。インヒビターのない血友病患者に対する止血治療ガイドライン2013に沿って、周術期の凝固因子製剤を投与した。凝固因子製剤のボーラス輸注では目標トラフ因子レベルを下回る時間帯が存在するため、持続静注を併用することとした。手術中も持続投与は継続した。手術中は止血に難渋することなく終了した。術後経過良好であり、術後再出血は認めなかった。血友病を合併したBasedow病に手術療法を選択した例は本邦では報告がなく症例の蓄積と検討が必要と考えられる。(著者抄録)

Publishing type：Research paper (scientific journal)  

骨・軟骨化生を伴う乳癌は,病巣内に骨化生や軟骨化生が認められる稀な腫瘍である.化生癌に分類されるため,トリプルネガティブ乳癌が多い.今回,Luminal Aサブタイプを呈した骨・軟骨化生を伴う乳癌の1例を経験した.69歳女性,右乳房腫瘤を主訴に当院紹介受診,右乳房上内側に約2cmの弾性硬の腫瘤を触知した.超音波検査では右乳腺A領域に1.5cm大の低エコー腫瘤を認め,針生検にて浸潤性乳管癌であった.右乳癌cT1N0M0 Stage Iと術前診断し,手術施行した(乳腺円状部分切除術).センチネルリンパ節に転移を認め,腋窩リンパ節郭清を追加した.線維化が高度であり,レース状の類骨様の基質産生を認め,骨・軟骨化生を伴う乳癌(pT1N1M0 Stage IIA)との最終診断に至った.ER強陽性,PgR強陽性,HER2陰性,Ki67 8%であり,Luminal Aサブタイプであった.(著者抄録)

Publishing type：Research paper (scientific journal)  

骨・軟骨化生を伴う乳癌は,病巣内に骨化生や軟骨化生が認められる稀な腫瘍である.化生癌に分類されるため,トリプルネガティブ乳癌が多い.今回,Luminal Aサブタイプを呈した骨・軟骨化生を伴う乳癌の1例を経験した.69歳女性,右乳房腫瘤を主訴に当院紹介受診,右乳房上内側に約2cmの弾性硬の腫瘤を触知した.超音波検査では右乳腺A領域に1.5cm大の低エコー腫瘤を認め,針生検にて浸潤性乳管癌であった.右乳癌cT1N0M0 Stage Iと術前診断し,手術施行した(乳腺円状部分切除術).センチネルリンパ節に転移を認め,腋窩リンパ節郭清を追加した.線維化が高度であり,レース状の類骨様の基質産生を認め,骨・軟骨化生を伴う乳癌(pT1N1M0 Stage IIA)との最終診断に至った.ER強陽性,PgR強陽性,HER2陰性,Ki67 8%であり,Luminal Aサブタイプであった.(著者抄録)

骨・軟骨化生を伴う乳癌は,病巣内に骨化生や軟骨化生が認められる稀な腫瘍である.化生癌に分類されるため,トリプルネガティブ乳癌が多い.今回,Luminal Aサブタイプを呈した骨・軟骨化生を伴う乳癌の1例を経験した.69歳女性,右乳房腫瘤を主訴に当院紹介受診,右乳房上内側に約2cmの弾性硬の腫瘤を触知した.超音波検査では右乳腺A領域に1.5cm大の低エコー腫瘤を認め,針生検にて浸潤性乳管癌であった.右乳癌cT1N0M0 Stage Iと術前診断し,手術施行した(乳腺円状部分切除術).センチネルリンパ節に転移を認め,腋窩リンパ節郭清を追加した.線維化が高度であり,レース状の類骨様の基質産生を認め,骨・軟骨化生を伴う乳癌(pT1N1M0 Stage IIA)との最終診断に至った.ER強陽性,PgR強陽性,HER2陰性,Ki67 8%であり,Luminal Aサブタイプであった.(著者抄録)

Publishing type：Research paper (scientific journal)  

Background: Intracystic papillary carcinoma (IPC) is defined as cancer that develops from the wall of a cyst in the breast. As breast cancer in men accounts for only 1% of all breast cancers, male IPC is an extremely rare form of the disease. The present case report examines IPC in a man, along with an in-depth literature discussion. Case presentation: A 64-year-old Japanese man noticed a mass in the right breast and sought medical attention. An elastic and soft neoplastic 3-cm lesion was palpated in the right papilla. As a 1-cm solid tumor with a gradual rise from the cyst wall was confirmed within the cyst, vacuum-assisted biopsy (VAB) was performed on that site. Pathological examination of the biopsy revealed heterotypic cells with an enlarged oval nucleus forming dense papillary structures mainly of vascular connective tissue component. Contrast-enhanced computed tomography (CT) confirmed thickening of the wall that protruded outside the cyst. The preoperative diagnosis was right breast cancer (male IPC) TisN0M0 stage 0 luminal B-like. Total mastectomy and sentinel lymph node biopsy were performed. In the excised specimen, a 4.0-cm unilocular cyst was found, along with a 1-cm solid tumor with a gradual rise from the cyst wall. Pathological diagnosis of the resected specimen shared similar characteristics with the solid tumor in the cyst: notably, an oval nucleus with histologically clear nucleolus and fine granular chromatin, cylindrically shaped heterotypic cells, and the presence of basophilic cells in the papillary growth with a thin stem of fibrovasculature as the axis. Some invasion of tumor cells into the interstitium was confirmed. As such, the final diagnosis was right breast cancer (male IPC) T2N0M0 stage IIA luminal B-like. The expression of hormone receptor (ER and PgR) was high, and endocrine therapy was initiated postoperatively (20mg/day tamoxifen). At the present time (3months postoperation), there has not been any evidence of metastasis. Conclusions: We reported a rare case of an IPC in the male breast, along with a literature review.

DOI： 10.1186/s12957-018-1318-5

PubMed

Publishing type：Research paper (scientific journal)  

Background/Aim: Eribulin mesylate (eribulin) is currently used for the treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress the epithelial-mesenchymal transition (EMT) of cancer cells and promote tumor vascular remodeling. In this study, we investigated the expression of markers for EMT and hypoxia in sets of clinical specimens collected before and after eribulin treatment to verify its unique mechanisms. Patients and Methods: The expression of markers for EMT and cellular hypoxia [E-cadherin, N-cadherin, vimentin, and carbonic anhydrase 9 (CA9)] was examined immunohistochemically in MBC tissues collected from 20 patients before and after chemotherapy with either eribulin (n=10) or paclitaxel (n=10). Results: An increase of E-cadherin and decrease of CA9 expression were observed in MBC tissues from patients with objective clinical responses to eribulin treatment. Patients with E-cadherin-positive conversion and CA9-negative conversion had significantly higher response rates (p=0.004 and p=0.024, respectively) and prolonged time to treatment failure (p=0.018 and p=0.038, respectively) than patients without changes in marker expression. Conclusion: Expression of EMT and hypoxia markers in clinical samples from patients with MBC was suppressed by eribulin treatment. The results provide additional clinical data on improved survival of patients treated with eribulin and the mechanism of response.

DOI： 10.21873/anticanres.12236

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

近年の画像診断の発達に伴いductal carcinoma in situ(DCIS)などの微小病変が発見される機会が増加している。当院では初回生検時に吸引式乳腺組織生検(vacuum-assisted biopsy:VAB)を使用しており、その有用性を検討した。2016年4〜12月の間にVABにより生検を行った32例を対象とした。生検結果の内訳は、乳癌10例、境界病変1例、良性病変が21例であった。平均腫瘍径は乳癌症例1.30cm、良性症例1.08cmと差は認められなかった。微細石灰化は乳癌症例の6例(60%)に認めたが、良性症例は1例(4%)とほとんど認めなかった。乳癌症例10例と良性症例1例に対して手術が施行され、病理結果の正診確定率は浸潤性乳管癌100%(4/4)、DCIS 83%(5/6)、良性病変が100%(1/1)と良好であった。腫瘍径の小さな腫瘍であっても、VABによる初回生検は正確な質的診断に寄与し、有用な生検方法であることが示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

In recent years, breast micro-lesions such as ductal carcinoma in situ (DCIS) were detected with progress of the image diagnosis. We investigated the usefulness of vacuum-assisted biopsy (VAB) for initial biopsy of breast tumors. We analyzed 32 cases of VAB performed for breast tumors. The pathological diagnosis of the biopsy specimens was malignant lesions in 10 cases, border-line lesions in 1 and benign lesions in 21 cases. 11 cases underwent surgery and the final histopathological diagnosis was the same in 10 of them. One case histopathology varied from DCIS to invasive ductal carcinoma (IDC). It was suggested that VAB at initial biopsy was a useful biopsy method.

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Background/Aim: Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m2/3weeks regimen. Patients and Methods: Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival. Results: Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks. Conclusion: Nab-PTX 175 mg/m2/3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment.

DOI： 10.21873/anticanres.12233

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

近年の画像診断の発達に伴いductal carcinoma in situ(DCIS)などの微小病変が発見される機会が増加している。当院では初回生検時に吸引式乳腺組織生検(vacuum-assisted biopsy:VAB)を使用しており、その有用性を検討した。2016年4〜12月の間にVABにより生検を行った32例を対象とした。生検結果の内訳は、乳癌10例、境界病変1例、良性病変が21例であった。平均腫瘍径は乳癌症例1.30cm、良性症例1.08cmと差は認められなかった。微細石灰化は乳癌症例の6例(60%)に認めたが、良性症例は1例(4%)とほとんど認めなかった。乳癌症例10例と良性症例1例に対して手術が施行され、病理結果の正診確定率は浸潤性乳管癌100%(4/4)、DCIS 83%(5/6)、良性病変が100%(1/1)と良好であった。腫瘍径の小さな腫瘍であっても、VABによる初回生検は正確な質的診断に寄与し、有用な生検方法であることが示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

&lt;p&gt;血友病を合併したBasedow病の症例は非常に稀である。今回われわれは甲状腺全摘出術を施行した１例を経験したので報告する。症例は25歳男性。内服コンプライアンスが不良であり，本人が手術を希望したため当院に紹介された。血友病に対しては，遺伝子組換え型血液凝固第Ⅷ因子製剤を生下時より定期注射しており，凝固因子活性検査第Ⅷ因子は１％未満で重症と判定されたが，日常生活には支障なかった。インヒビターのない血友病患者に対する止血治療ガイドライン2013に沿って，周術期の凝固因子製剤を投与した。凝固因子製剤のボーラス輸注では目標トラフ因子レベルを下回る時間帯が存在するため，持続静注を併用することとした。手術中も持続投与は継続した。手術中は止血に難渋することなく終了した。術後経過良好であり，術後再出血は認めなかった。血友病を合併したBasedow病に手術療法を選択した例は本邦では報告がなく症例の蓄積と検討が必要と考えられる。&lt;/p&gt;

DOI： 10.11226/jaesjsts.35.1_61

CiNii Article

Publishing type：Research paper (scientific journal)  

Background: Studies have found that patients with cancer exhibit abnormal leukocyte fractions, such as elevated neutrophil count and diminished lymphocyte count, and that the neutrophil-to-lymphocyte ratio (NLR) provides a surrogate marker for prognosis and response to treatment of patients after radical surgery for several different types of cancer. However, few reports have addressed the association between the NLR and response to endocrine therapy. In this study, we carried out a clinical investigation to confirm whether or not the NLR predicted the response to endocrine therapy of stage IV breast cancer. Patients and Methods: The study subjects were 34 patients who underwent endocrine therapy as initial drug therapy for stage IV breast cancer. The correlation between NLR and prognosis, including the efficacy of endocrine therapy, was evaluated retrospectively. Results: Among the 34 patients, the NLR was high in 10 (29.4%) and low in 24 (70.6%). In analysis of outcomes, the group with low NLR had a significant prolongation of progression-free survival (p=0.003), time to treatment failure (p=0.031), and overall survival (p=0.013) compared to the group with high NLR. Univariate analysis of progression-free survival found that responding to treatment [hazard ratio (HR)=4.310, p=0.004] and low NLR (HR=3.940, p=0.016) were factors associated with a favorable prognosis. Multivariate analysis also showed that responding to treatment (HR=4.329, p=0.006) and low NLR (HR=3.930, p=0.008) were independent factors associated with a favorable prognosis. Conclusion: Our results suggested that the NLR may represent a predictive marker for response to endocrine therapy in stage IV breast cancer.

DOI： 10.21873/invivo.11292

PubMed

Publishing type：Research paper (scientific journal)  

<p>A 69-year-old woman referred to our hospital because of palpation of right breast lump. The tumor was about 2 cm in size in the upper outer quadrant of right breast. Mammary gland ultrasonography findings revealed a 1.5-cm hypoechoic mass with rupture of the anterior boundary line in the right mammary gland A area. The tumor was diagnosed as invasive ductal carcinoma with core needle biopsy. Under a diagnosis of right breast cancer with cT1N0M0 Stage Ⅰ, partial mastectomy and sentinel lymph node biopsy were performed. Axially lymph node metastasis was revealed and axially lymph node dissection was performed. Histopathological diagnosis was breast cancer with cartilaginous and osseous metaplasia with pT1N1M0 Stage ⅡA. Immunohistrochemical study revealed ER+, PgR+, HER2-, Ki67 low and diagnosed as luminal A subtype. Generally, breast cancer with cartilaginous and osseous metaplasia classified into triple negative subtype. However this case was classified into luminal A subtype. We reported a rare case with a review of literature.</p>

DOI： 10.4030/jjcs.43.13

CiNii Article

Publishing type：Research paper (scientific journal)  

Background/Aim: The anticancer immune response has been reported to contribute to the success of chemotherapy. The aim of this study was to evaluate the significance of the measurement of tumor-infiltrating lymphocytes (TILs) in the primary tumor using the method proposed by the International TILs Working Group as a prognostic marker of chemotherapeutic outcomes in patients with stage IV colorectal cancer (CRC). Patients and Methods: A total of 57 patients with stage IV CRC who underwent palliative chemotherapy after resection of the primary tumor were enrolled. Hematoxylin and eosin (H-E)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by measuring the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. Immunohistochemistry for CD8 was also performed, and the number of immunoreactive cytotoxic T-lymphocytes (CTLs) at the invasive margin was counted. Results: Thirty patients were classified into the high-TILs group, and 27 patients were classified into the low-TILs group. The high-TILs group had a significantly higher chemotherapeutic response rate (79.3% vs. 48.1%, p=0.025) and better progression-free survival (median survival time: 10.1 m vs. 7.3 m, p=0.0133) than the low-TILs group. Furthermore, the high-TILs group had a significantly better overall survival than the low-TILs group (median survival time: 35.5 m vs. 22.4 m, p=0.0221). The density of TILs evaluated using the H-E-stained sections showed a strong association with the number of CTLs (p&lt
0.001). Conclusion: The measurement of TILs in the primary tumor using the method proposed by the International TILs Working Group can be used as a prognostic marker of the clinical effectiveness of palliative chemotherapy in patients with stage IV CRC.

DOI： 10.21873/invivo.11218

PubMed

Publishing type：Research paper (scientific journal)  

Background: The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses can be evaluated with tumor-infiltrating lymphocytes (TILs), which has frequently been verified clinically. On the other hand, residual cancer burden (RCB) evaluation has been shown to be a useful predictor of survival after neoadjuvant chemotherapy (NAC). In this study, RCB and TILs evaluations were combined to produce an indicator that we have termed "RCB-TILs", and its clinical application to NAC for breast cancer was verified by subtype-stratified analysis. Methods: A total of 177 patients with breast cancer were treated with NAC. The correlation between RCB and TILs evaluated according to the standard method, and prognosis, including the efficacy of NAC, was investigated retrospectively. The RCB and TILs evaluations were combined to create the "RCB-TILs". Patients who were RCB-positive and had high TILs were considered RCB-TILs-positive, and all other combinations were RCB-TILs-negative. Results: On multivariable analysis, being RCB-TILs-positive was an independent factor for recurrence after NAC in all patients (p &lt
0.001, hazard ratio = 0.048), triple-negative breast cancer (TNBC) patients (p = 0.018, hazard ratio = 0.041), HER2-positive breast cancer (HER2BC) patients (p = 0.036, hazard ratio = 0.134), and hormone receptor-positive breast cancer (HRBC) patients (p = 0.002, hazard ratio = 0.081). Conclusions: The results of the present study suggest that RCB-TILs is a significant predictor for breast cancer recurrence after NAC and may be a more sensitive indicator than TILs alone.

DOI： 10.1186/s12885-017-3927-8

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Adenoma of the nipple is a rare benign tumor, and it is important to distinguish from Paget's disease or breast cancer. A 45- year-old woman had found induration under the right areola before 2 months and visited our hospital. Ultrasonography showed a 2.4 cm solid tumor in a cystic lesion, which had high blood flow in E area of the right mammary gland. The tumor suspected as duct papillomatosis by core needle biopsy. No metastasis lesion was found by computed tomography and bone scintigraphy. But magnetic resonance imaging showed as a marginally clear tumor with contrast enhanced findings that were relatively early reinforced and prolonged. Because there was a possibility of malignancy based on these findings, tumorectomy was done with patient consent. Histological examination revealed usual ductal hyperplasia(duct papillomatosis)and no malignancy. No recurrence was seen for a year after operation. When diagnosing a tumor under areola, be careful not to misdiagnose malignancy.

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 67-year-old female was referred to our hospital because she was pointed out mass in her right breast by her previous doctor. Core needle biopsy examination was performed at that time which revealed invasive ductal carcinoma. There'reno palpable masses in her breast or any superficial lymph nodes on her visiting our hospital. Breast ultrasonography images showed multiple nodules in C area of right breast. Breast enhanced MRI image revealed multiple enhanced nodules which showed rapid arising and plateau or slowly decreasing pattern in time intensity curve. CT scan and bone scintigraphy revealed no distant metastasis. Based on these findings, the case was diagnosed as right breast cancer, cT1N0M0, Stage I . For this case, we performed right mastectomy and sentinel lymph node biopsy. The pathological findings was ductal carcinoma in situ (DCIS)accompanied by sclerosing adenosis. Though we didn't perform adjuvant chemotherapy, she has been alive without recurrence for 6 years. Because it's difficult to make correct diagnosis with small specimen collected by core needle biopsy, we should take DCIS in sclerosing adenosis into consideration to prevent overdiagnosis.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

The rate of local recurrence after mastectomy is reportedly similar to that of one-stage reconstruction. Most recurrences are in the skin or chest wall, while recurrence in the reconstructed breast is rare and the causes are uncertain. We report a case of a 42-year-old female who underwent partial mastectomy for left breast cancer with cT4aN0M1(PUL), cStage IV after endocrine therapy 3 years ago. Histopathological diagnosis was solid-tubular carcinoma. She had been treated with only endocrine therapy but diagnosed with local recurrence in the left breast. She underwent total mastectomy and rectus abdominis musculocutaneous flap reconstruction. Partial flap necrosis occurred following conservative therapy. She was accordingly treated with anastrozole and GnRH agonist. A mass approximately 1.5 cm in size was palpated inside of the reconstructed breast. As such, she was diagnosed with recurrence in the reconstructed breast through ultrasound biopsy. She underwent partial resection of the left precordial tumor, and histopathological examination revealed scirrhous cancer. She is currently well without any recurrence.

PubMed

J-GLOBAL

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 46-year-old woman visited our hospital with a chief complaint of a mass in the right breast. Breast ultrasonography revealed a hypoechoic area with an indistinct border on the right breast, and right axillary lymph node swelling. A core needle biopsy revealed invasive ductal carcinoma, and the diagnosis was right breast cancer, cT2N2M0, Stage III A, HER2-enriched type. We administered 4 courses of FEC followed by weekly paclitaxel plus trastuzumab. After the treatment, she had eruption and erythema on the face, precordium and forearm. Though dermatomyositis associated cancer was suspected, a definite diagnosis was not made. However, skin symptoms were improved significantly after mastectomy, suggesting that she had dermatomyositis. For the skin symptom during breast cancer treatment, the examination should be made with the possibility of the adverse effect of chemotherapy and dermatomyositis associated cancer.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 64-year-old woman visited hospital with a chief complaint of a nodule at the left neck skin. Skin biopsy revealed adenocarcinoma, and the diagnosis was skin metastasis of unknown primary origin. Positron emission tomography and computed tomography showed multiple bone and lymph node metastasis, left breast tumor, bladder tumor, and hydronephrosis. A needle biopsy of breast revealed invasive ductal carcinoma, and transurethral biopsy of bladder revealed adenocarcinoma. The findings were similar to those for the breast and the expression pattern of estrogen-receptor was the same. We diagnosed her with breast cancer and bladder metastasis. We administered systemic chemotherapy, however she died 10 days later. Bladder metastasis of breast cancer is rarely encountered in clinical practice and is often accompanied by life threatening symptoms. Careful histopathological examinations and rapid systemic chemotherapy are significant.

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

症例は64歳、女性。左頸部皮膚結節を自覚し近医を受診、皮膚生検で腺癌と診断され、原発不明癌皮膚転移の精査加療目的に当院紹介となった。画像検査で多発骨転移・多発リンパ節転移とともに左乳腺腫瘤と膀胱腫瘤を認め、両側水腎症も伴っていた。左乳腺腫瘤の針生検では浸潤性乳管癌、膀胱鏡下の膀胱腫瘍生検では腺癌の診断であった。乳腺腫瘍と膀胱腫瘍の病理組織像が類似し、腺癌、ホルモン受容体陽性であることなどを考慮し、左乳癌膀胱転移、cT2N2M1(OSS、LYM、SKI、BLA)、stage IV(Luminal-HER2 subtype)との診断に至った。腎瘻を造設し水腎症を解除した上で、化学療法(trastuzumab、pertuzumab、docetaxel)を開始した。しかし全身状態の増悪を来し、治療開始後10日後に死亡した。乳癌からの膀胱転移はまれであり、発見時に高度な進行を伴う場合が考えられる。正確な治療前診断を進め、迅速に全身療法を開始することが望まれる。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は46歳、女性。右乳房腫瘤を自覚し近医を受診、精査加療目的に当院紹介となった。超音波検査にて右乳腺CD領域に2.8×2.7×2.2cm大の低エコー腫瘤が確認され、同部位の針生検にて浸潤性乳管癌(ER陰性、PgR陰性、HER2強陽性、Ki-67高発現)であった。CT検索において患側腋窩にリンパ節転移が認められたために、治療前診断は右乳癌、cT2N2M0、Stage IIIA、HER2-enriched typeとした。術前化学療法(NAC)としてFEC followed by weekly paclitaxel+trastuzumabを施行したところ、治療開始後に顔面・前胸部・前腕に紅斑や皮疹を認めた。腫瘍随伴性皮膚筋炎が疑われたが確定診断には至らず、化学療法に伴う皮膚炎を考えた。しかしながら、NAC後に乳房切除を施行したところ皮膚症状が著明に改善したために腫瘍随伴性皮膚筋炎であった可能性も考慮される。乳癌治療中の皮膚症状に対しては、化学療法の副作用とともに腫瘍随伴性皮膚筋炎を念頭に精査を進める必要がある。(著者抄録)

Publishing type：Research paper (scientific journal)  

腫瘍径5mm以下のT1a乳癌は微小病変として扱われ、腋窩リンパ節転移を来すことはまれだと考えられている。症例は52歳、女性。検診マンモグラフィにて異常陰影を指摘され当院を紹介された。乳腺超音波検査にて、左乳腺AC領域に4mm大の石灰化を伴う辺縁不整・境界不明瞭な低エコー腫瘤を認め、吸引式乳腺組織生検にて浸潤性乳管癌との診断に至った。全身検索では遠隔転移を認めず、左乳癌、cT1aN0M0、stage I、Luminal A likeにて手術(乳腺円状部分切除術およびセンチネルリンパ節生検)を施行した。術中、提出したリンパ節に4mm径の転移性病変が確認され、腋窩リンパ節郭清(level II)を追加した。摘出標本の主病巣の腫瘍径は4mmのpT1aであり、病理診断で乳頭腺管癌であった。その後、残存乳腺に50Gyの放射線照射および内分泌療法(tamoxifen 20mg/5年間)を行い、術後5年にて転移・再発は認められていない。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は67歳、女性。自覚症状はなく、近医の乳腺超音波検査にて右乳腺腫瘤を指摘され、針生検にて浸潤性乳管癌との診断を受け当院紹介となった。受診時現症では視触診にて乳房腫瘤や体表リンパ節は触知せず、乳腺超音波検査にて右C領域に最大径9.8mm大の多発する小結節を認めた。CTおよび骨シンチグラフィによる全身検索では、遠隔転移は認められなかった。造影MRIでは、右乳腺上外側域の結節に相応し濃染結節が多発していた。術前診断は右乳癌、cT1N0M0、Stage Iであり、単純乳房切除術およびセンチネルリンパ節生検を施行した。病理診断では硬化性腺症内の上皮に異型が認められ、硬化性腺症内非浸潤性乳管癌(ductal carcinoma in situ:DCIS)との診断に至った。術後6年にて無再発生存中である。術前診断に際しては硬化性腺症内DCISも念頭に置いて、浸潤癌と過剰診断しないように注意を払う必要があると考えられた。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は71歳、女性。皮膚黄染と右季肋部痛を主訴に近医を受診した。腹部CTや血液検査により、十二指腸乳頭部が閉塞起点となる閉塞性黄疸と考えられた。内視鏡による精査にて十二指腸乳頭部癌と診断され、精査加療目的に当院へ紹介となった。術前CT検査では、両肺野および左乳腺に腫瘤影、左腋窩にもリンパ節腫大が認められた。乳腺超音波検査では、左乳腺ECD領域に1.7cm大の不整形腫瘤を認め、針生検にて原発性乳癌と診断された。さらに肺病変の原発巣精査目的にて、胸腔鏡下右肺部分切除術を施行、原発性肺腺癌との診断に至った。骨シンチグラフィにて多発骨転移も確認された。以上より、骨転移を伴う高度進行性の同時性三重複癌と診断した。今回われわれは、同時性に乳癌・十二指腸癌・肺癌の三重複癌を認めたまれな1例を経験したので、文献的考察を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

乳房再建後の局所再発については、同側皮膚や胸壁において非再建乳房と同等の頻度で発症するとされているが、再建乳房内からの局所再発の報告は少なく発生原因など不明な点が多い。症例は42歳、女性。3年前に左乳癌、cT4aN0M1(PUL)、cStage IV、Luminal A likeに対して内分泌療法(tamoxifen)を行ったところ、著明に原発巣の縮小および肺転移病変の消失が認められたため乳房温存手術を行った。病理診断は充実腺管癌であった。内分泌療法単独にて治療を継続していたが、翌年に残存乳腺から局所再発を発症した。乳房全摘および腹直筋皮弁による再建術を行ったが、腹直筋皮弁の部分壊死を来したため保存的に加療した。全身療法としての内分泌療法はanastrozoleおよびGnRH agonistへと変更した。今回、再建乳房内側に約1.5cm大の硬結を触知し、超音波ガイド下の生検にて再建乳房からの局所再発と診断された。左前胸部腫瘤切除術を施行し、病理所見は硬癌であった。その後は再発なく外来通院中である。(著者抄録)

Publishing type：Research paper (scientific journal)  

乳頭部腺腫はまれな良性疾患であるが、悪性腫瘍との鑑別が重要となる。症例は45歳、女性。2ヵ月前から右乳頭部にしこりを自覚し近医を受診、精査加療目的にて当院へ紹介された。超音波検査にて右乳房E領域に2.4cm大で血流豊富な類円形の嚢胞内腫瘤を認め、針生検にてduct papillomatosisの疑いであった。CTや骨シンチグラフィでは、遠隔転移は確認されなかった。MRIでは右乳頭部に早期に造影され、効果が遷延する辺縁明瞭な腫瘤性病変を認めた。これらの画像所見より悪性が否定できなかったため、確定診断および治療目的にて右乳腺腫瘤摘出術を施行した。病理組織診断ではusual ductal hyperplasia(duct papillomatosis)であり、悪性所見は認められなかった。今回われわれは、術前精査にて乳頭部乳癌が疑われ、最終診断では乳頭部腺腫であった1例を経験した。(著者抄録)

Publishing type：Research paper (scientific journal)  

乳腺腫瘍に対する質的診断は、針生検(core needle biopsy:CNB)が第一選択とされるが、腫瘤を形成せずまばらな病変や線維化の強い硬化性病変では、組織診断を得るために必要な組織量を十分に採取できないこともある。そのため吸引式乳腺組織生検による豊富な生検材料が求められるが、当施設ではEnCor ENSPIREシステムを導入している。2015年1月〜2016年5月の間にEnCor ENSPIREシステムで生検施行した24例を対象とした。悪性と診断された病変は12例(50.0%)であった。うち浸潤性乳管癌(IDC)7例(29.2%)、非浸潤性乳管癌(DCIS)が5例(20.8%)であった。悪性との診断に至らなかった12例のうち、異形乳管過形成(ADH)3例(12.5%)、乳管内乳頭腫(IDP)が3例(12.5%)であった。また、6例(25.0%)では確定診断目的にて腫瘍摘出がなされていた。術後出血などの偶発症は認められなかった。EnCor ENSPIREシステムを用いた乳腺組織生検は、検体採取量が多く優れた診断能をもち、正確な治療前診断への寄与が期待できる。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

近年、癌治療のアウトカム指標の一つとしてquality of life(QOL)の重要性が再認識されつつある。癌の疾患特異的尺度として、本邦ではQOL-ACDが使用されることが多い。今回われわれは、QOL-ACDを用いた乳癌術前化学療法(neoadjuvant chemotherapy:NAC)後の予後解析を行った。対象は乳癌NAC症例228例とし、QOL-ACDを用いて後方視的に抗腫瘍効果や予後との相関について検討した。高QOL-ACD群208例(91.2%)は、低QOL-ACD群20例(8.8%)と比較して、NAC後の無病生存期間(p=0.009、logrank)および全生存期間(p=0.040、logrank)の延長を認めた。さらにNAC後は、NAC前と比較して包括的評価スコアの低下を認めるものの、抗腫瘍効果との相関を認めなかった。下位評価尺度において、病理学的完全奏効(pathological complete response:pCR)症例は、non-pCR症例と比較して、「医療に対する満足感と病気に対するコーピング」尺度の変化が低い結果であったが、「身体症状・疼痛」尺度では差は認められなかった。乳癌NAC症例において、QOL-ACDはNAC後の予

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

We investigated into association of quality of life(QOL)and prognosis of breast cancer patients who underwent neoadjuvant chemotherapy(NAC). We retrospectively studied 228 patients with breast cancer who were performed NAC during a period between 2007 and 2015. TheQ OL score was measured with"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs(QOL-ACD)". We evaluate association between QOL score with antitumor effect and prognosis. Changes in the QOL score between before and after NAC were compared as well. We divided 2 groups by QOL-ACD scoreinto high and low groups. Therapeautic effect of NAC on 75 patients were pathological complete response(pCR). QOL-ACD score was not significantly associated with pCR rate in both high and low groups(p=0.199). High group was significantly associated with higher survival rate in both of disease free survival(p=0.009, logrank)and overall survival(p=0.040, logrank). QOLACD score decreased after NAC in both of pCR and non-pCR patients. In conclusion, QOL evaluation using QOL-ACD could be an indicator of breast cancer patients' prognosis who underwent NAC.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

We investigated the usefulness of vacuum-assisted biopsy(VAB)using the EnCor ENSPIRE®system for initial biopsy of breast tumors. We analyzed 24 cases of VAB using the EnCor ENSPIRE®system performed for breast tumors. Of 24 mammary lesions, 12 cases(50.0%)were diagnosed as malignant. Among them, 7 cases(29.2%)were invasive ductal carcinoma(IDC) and 5 cases(20.8%)were ductal carcinoma in situ(DCIS). Six cases required tumor resection for definitive diagnosis; 1 case was diagnosed with IDC, 2 cases with DCIS, 2 cases with intraductal papilloma(IDP), and 1 case with atypical ductal hyperplasia( ADH). Moreover, EnCor ENSPIRE®system biopsy was performed in 15 cases because malignancy could not be diagnosed using core needle biopsy. There were 4 cases of IDC, 4 cases of DCIS, 2 cases of IDP, 2 cases of usual ductal hyperplasia, and 2 cases of ADH. There were no complications due to a series of procedures. We believe that the EnCor ENSPIRE®system is an effective technique having both convenience and great diagnostic accuracy.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A breast cancer with tumors smaller than or equal to 5mm in diameter is treated as a microscopic lesion and axially lymph node metastasis is considered to be rare. A 52-year-old female was found to have an abnormal shadow on mammography. An ultrasonography revealed a poorly defined and irregular shaped mass with calcification, 4mm in diameter, in the AC area of her left breast. We performed vacuum-assisted biopsy and diagnosed with invasive ductal carcinoma. Under a preoperative diagnosis of left breast cancer with cT1aN0M0, stage I , Luminal A like, we underwent partial mastectomy with sentinel lymph node biopsy. The intraoperative consultation suggested sentinel lymph node metastasis and we therefore performed level II axillary lymph node dissection. The size of the tumor was 4mm and diagnosed with pT1a breast cancer. Histopathological diagnosis was papillotubular carcinoma. Radiotherapy was performed(total: 50 Gy)followed by endocrine therapy (tamoxifen). She is alive without recurrence and metastasis 5 years after surgery.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 71-year-old woman visited her nearby hospital because jaundice and right hypochondralgia. She was diagnosed as obstructive jaundice due to duodenal papillary carcinoma and was introduced to our hospital. Chest computed tomography showed some tumors in both lung and left breast, then the breast tumor was diagnosed as primary breast cancer by needle biopsy. Since it was difficult to distinguish whether multiple tumor of lung was primary lung cancer or metastasis, right pulmonary partial resection using a thoracoscope was performed. In histopathological examination, it was diagnosed as adenocarcinoma of the pulmonary primary. Multiple bone metastases were also showed by bone scintigraphy. Therefore, the diagnosis was advanced progressive synchronous triple cancer with bone metastasis. She did not hope for aggressive treatment, it has now reached observation of no treatment. In recent years, due to advances in diagnostic technology reports of duplicated cancer cases are increasing, but I have experienced a case of extremely rare triple cancer of the breast, duodenal and lung.

PubMed

Publishing type：Research paper (scientific journal)  

症例は64歳、女性。左頸部皮膚結節を自覚し近医を受診、皮膚生検で腺癌と診断され、原発不明癌皮膚転移の精査加療目的に当院紹介となった。画像検査で多発骨転移・多発リンパ節転移とともに左乳腺腫瘤と膀胱腫瘤を認め、両側水腎症も伴っていた。左乳腺腫瘤の針生検では浸潤性乳管癌、膀胱鏡下の膀胱腫瘍生検では腺癌の診断であった。乳腺腫瘍と膀胱腫瘍の病理組織像が類似し、腺癌、ホルモン受容体陽性であることなどを考慮し、左乳癌膀胱転移、cT2N2M1(OSS、LYM、SKI、BLA)、stage IV(Luminal-HER2 subtype)との診断に至った。腎瘻を造設し水腎症を解除した上で、化学療法(trastuzumab、pertuzumab、docetaxel)を開始した。しかし全身状態の増悪を来し、治療開始後10日後に死亡した。乳癌からの膀胱転移はまれであり、発見時に高度な進行を伴う場合が考えられる。正確な治療前診断を進め、迅速に全身療法を開始することが望まれる。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は46歳、女性。右乳房腫瘤を自覚し近医を受診、精査加療目的に当院紹介となった。超音波検査にて右乳腺CD領域に2.8×2.7×2.2cm大の低エコー腫瘤が確認され、同部位の針生検にて浸潤性乳管癌(ER陰性、PgR陰性、HER2強陽性、Ki-67高発現)であった。CT検索において患側腋窩にリンパ節転移が認められたために、治療前診断は右乳癌、cT2N2M0、Stage IIIA、HER2-enriched typeとした。術前化学療法(NAC)としてFEC followed by weekly paclitaxel+trastuzumabを施行したところ、治療開始後に顔面・前胸部・前腕に紅斑や皮疹を認めた。腫瘍随伴性皮膚筋炎が疑われたが確定診断には至らず、化学療法に伴う皮膚炎を考えた。しかしながら、NAC後に乳房切除を施行したところ皮膚症状が著明に改善したために腫瘍随伴性皮膚筋炎であった可能性も考慮される。乳癌治療中の皮膚症状に対しては、化学療法の副作用とともに腫瘍随伴性皮膚筋炎を念頭に精査を進める必要がある。(著者抄録)

Publishing type：Research paper (scientific journal)  

腫瘍径5mm以下のT1a乳癌は微小病変として扱われ、腋窩リンパ節転移を来すことはまれだと考えられている。症例は52歳、女性。検診マンモグラフィにて異常陰影を指摘され当院を紹介された。乳腺超音波検査にて、左乳腺AC領域に4mm大の石灰化を伴う辺縁不整・境界不明瞭な低エコー腫瘤を認め、吸引式乳腺組織生検にて浸潤性乳管癌との診断に至った。全身検索では遠隔転移を認めず、左乳癌、cT1aN0M0、stage I、Luminal A likeにて手術(乳腺円状部分切除術およびセンチネルリンパ節生検)を施行した。術中、提出したリンパ節に4mm径の転移性病変が確認され、腋窩リンパ節郭清(level II)を追加した。摘出標本の主病巣の腫瘍径は4mmのpT1aであり、病理診断で乳頭腺管癌であった。その後、残存乳腺に50Gyの放射線照射および内分泌療法(tamoxifen 20mg/5年間)を行い、術後5年にて転移・再発は認められていない。(著者抄録)

Publishing type：Research paper (scientific journal)  

近年、癌治療のアウトカム指標の一つとしてquality of life(QOL)の重要性が再認識されつつある。癌の疾患特異的尺度として、本邦ではQOL-ACDが使用されることが多い。今回われわれは、QOL-ACDを用いた乳癌術前化学療法(neoadjuvant chemotherapy:NAC)後の予後解析を行った。対象は乳癌NAC症例228例とし、QOL-ACDを用いて後方視的に抗腫瘍効果や予後との相関について検討した。高QOL-ACD群208例(91.2%)は、低QOL-ACD群20例(8.8%)と比較して、NAC後の無病生存期間(p=0.009、logrank)および全生存期間(p=0.040、logrank)の延長を認めた。さらにNAC後は、NAC前と比較して包括的評価スコアの低下を認めるものの、抗腫瘍効果との相関を認めなかった。下位評価尺度において、病理学的完全奏効(pathological complete response:pCR)症例は、non-pCR症例と比較して、「医療に対する満足感と病気に対するコーピング」尺度の変化が低い結果であったが、「身体症状・疼痛」尺度では差は認められなかった。乳癌NAC症例において、QOL-ACDはNAC後の予後予測として有用な指標であることが示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

症例は64歳、女性。左頸部皮膚結節を自覚し近医を受診、皮膚生検で腺癌と診断され、原発不明癌皮膚転移の精査加療目的に当院紹介となった。画像検査で多発骨転移・多発リンパ節転移とともに左乳腺腫瘤と膀胱腫瘤を認め、両側水腎症も伴っていた。左乳腺腫瘤の針生検では浸潤性乳管癌、膀胱鏡下の膀胱腫瘍生検では腺癌の診断であった。乳腺腫瘍と膀胱腫瘍の病理組織像が類似し、腺癌、ホルモン受容体陽性であることなどを考慮し、左乳癌膀胱転移、cT2N2M1(OSS、LYM、SKI、BLA)、stage IV(Luminal-HER2 subtype)との診断に至った。腎瘻を造設し水腎症を解除した上で、化学療法(trastuzumab、pertuzumab、docetaxel)を開始した。しかし全身状態の増悪を来し、治療開始後10日後に死亡した。乳癌からの膀胱転移はまれであり、発見時に高度な進行を伴う場合が考えられる。正確な治療前診断を進め、迅速に全身療法を開始することが望まれる。(著者抄録)

症例は46歳、女性。右乳房腫瘤を自覚し近医を受診、精査加療目的に当院紹介となった。超音波検査にて右乳腺CD領域に2.8×2.7×2.2cm大の低エコー腫瘤が確認され、同部位の針生検にて浸潤性乳管癌(ER陰性、PgR陰性、HER2強陽性、Ki-67高発現)であった。CT検索において患側腋窩にリンパ節転移が認められたために、治療前診断は右乳癌、cT2N2M0、Stage IIIA、HER2-enriched typeとした。術前化学療法(NAC)としてFEC followed by weekly paclitaxel+trastuzumabを施行したところ、治療開始後に顔面・前胸部・前腕に紅斑や皮疹を認めた。腫瘍随伴性皮膚筋炎が疑われたが確定診断には至らず、化学療法に伴う皮膚炎を考えた。しかしながら、NAC後に乳房切除を施行したところ皮膚症状が著明に改善したために腫瘍随伴性皮膚筋炎であった可能性も考慮される。乳癌治療中の皮膚症状に対しては、化学療法の副作用とともに腫瘍随伴性皮膚筋炎を念頭に精査を進める必要がある。(著者抄録)

腫瘍径5mm以下のT1a乳癌は微小病変として扱われ、腋窩リンパ節転移を来すことはまれだと考えられている。症例は52歳、女性。検診マンモグラフィにて異常陰影を指摘され当院を紹介された。乳腺超音波検査にて、左乳腺AC領域に4mm大の石灰化を伴う辺縁不整・境界不明瞭な低エコー腫瘤を認め、吸引式乳腺組織生検にて浸潤性乳管癌との診断に至った。全身検索では遠隔転移を認めず、左乳癌、cT1aN0M0、stage I、Luminal A likeにて手術(乳腺円状部分切除術およびセンチネルリンパ節生検)を施行した。術中、提出したリンパ節に4mm径の転移性病変が確認され、腋窩リンパ節郭清(level II)を追加した。摘出標本の主病巣の腫瘍径は4mmのpT1aであり、病理診断で乳頭腺管癌であった。その後、残存乳腺に50Gyの放射線照射および内分泌療法(tamoxifen 20mg/5年間)を行い、術後5年にて転移・再発は認められていない。(著者抄録)

症例は67歳、女性。自覚症状はなく、近医の乳腺超音波検査にて右乳腺腫瘤を指摘され、針生検にて浸潤性乳管癌との診断を受け当院紹介となった。受診時現症では視触診にて乳房腫瘤や体表リンパ節は触知せず、乳腺超音波検査にて右C領域に最大径9.8mm大の多発する小結節を認めた。CTおよび骨シンチグラフィによる全身検索では、遠隔転移は認められなかった。造影MRIでは、右乳腺上外側域の結節に相応し濃染結節が多発していた。術前診断は右乳癌、cT1N0M0、Stage Iであり、単純乳房切除術およびセンチネルリンパ節生検を施行した。病理診断では硬化性腺症内の上皮に異型が認められ、硬化性腺症内非浸潤性乳管癌(ductal carcinoma in situ:DCIS)との診断に至った。術後6年にて無再発生存中である。術前診断に際しては硬化性腺症内DCISも念頭に置いて、浸潤癌と過剰診断しないように注意を払う必要があると考えられた。(著者抄録)

症例は71歳、女性。皮膚黄染と右季肋部痛を主訴に近医を受診した。腹部CTや血液検査により、十二指腸乳頭部が閉塞起点となる閉塞性黄疸と考えられた。内視鏡による精査にて十二指腸乳頭部癌と診断され、精査加療目的に当院へ紹介となった。術前CT検査では、両肺野および左乳腺に腫瘤影、左腋窩にもリンパ節腫大が認められた。乳腺超音波検査では、左乳腺ECD領域に1.7cm大の不整形腫瘤を認め、針生検にて原発性乳癌と診断された。さらに肺病変の原発巣精査目的にて、胸腔鏡下右肺部分切除術を施行、原発性肺腺癌との診断に至った。骨シンチグラフィにて多発骨転移も確認された。以上より、骨転移を伴う高度進行性の同時性三重複癌と診断した。今回われわれは、同時性に乳癌・十二指腸癌・肺癌の三重複癌を認めたまれな1例を経験したので、文献的考察を加えて報告する。(著者抄録)

乳房再建後の局所再発については、同側皮膚や胸壁において非再建乳房と同等の頻度で発症するとされているが、再建乳房内からの局所再発の報告は少なく発生原因など不明な点が多い。症例は42歳、女性。3年前に左乳癌、cT4aN0M1(PUL)、cStage IV、Luminal A likeに対して内分泌療法(tamoxifen)を行ったところ、著明に原発巣の縮小および肺転移病変の消失が認められたため乳房温存手術を行った。病理診断は充実腺管癌であった。内分泌療法単独にて治療を継続していたが、翌年に残存乳腺から局所再発を発症した。乳房全摘および腹直筋皮弁による再建術を行ったが、腹直筋皮弁の部分壊死を来したため保存的に加療した。全身療法としての内分泌療法はanastrozoleおよびGnRH agonistへと変更した。今回、再建乳房内側に約1.5cm大の硬結を触知し、超音波ガイド下の生検にて再建乳房からの局所再発と診断された。左前胸部腫瘤切除術を施行し、病理所見は硬癌であった。その後は再発なく外来通院中で

乳頭部腺腫はまれな良性疾患であるが、悪性腫瘍との鑑別が重要となる。症例は45歳、女性。2ヵ月前から右乳頭部にしこりを自覚し近医を受診、精査加療目的にて当院へ紹介された。超音波検査にて右乳房E領域に2.4cm大で血流豊富な類円形の嚢胞内腫瘤を認め、針生検にてduct papillomatosisの疑いであった。CTや骨シンチグラフィでは、遠隔転移は確認されなかった。MRIでは右乳頭部に早期に造影され、効果が遷延する辺縁明瞭な腫瘤性病変を認めた。これらの画像所見より悪性が否定できなかったため、確定診断および治療目的にて右乳腺腫瘤摘出術を施行した。病理組織診断ではusual ductal hyperplasia(duct papillomatosis)であり、悪性所見は認められなかった。今回われわれは、術前精査にて乳頭部乳癌が疑われ、最終診断では乳頭部腺腫であった1例を経験した。(著者抄録)

乳腺腫瘍に対する質的診断は、針生検(core needle biopsy:CNB)が第一選択とされるが、腫瘤を形成せずまばらな病変や線維化の強い硬化性病変では、組織診断を得るために必要な組織量を十分に採取できないこともある。そのため吸引式乳腺組織生検による豊富な生検材料が求められるが、当施設ではEnCor ENSPIREシステムを導入している。2015年1月〜2016年5月の間にEnCor ENSPIREシステムで生検施行した24例を対象とした。悪性と診断された病変は12例(50.0%)であった。うち浸潤性乳管癌(IDC)7例(29.2%)、非浸潤性乳管癌(DCIS)が5例(20.8%)であった。悪性との診断に至らなかった12例のうち、異形乳管過形成(ADH)3例(12.5%)、乳管内乳頭腫(IDP)が3例(12.5%)であった。また、6例(25.0%)では確定診断目的にて腫瘍摘出がなされていた。術後出血などの偶発症は認められなかった。EnCor ENSPIREシステムを用いた乳腺組織生検は、検体採取量が多く優れた診断能をもち、正確な治療前診断への寄与が期待できる。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

近年、癌治療のアウトカム指標の一つとしてquality of life(QOL)の重要性が再認識されつつある。癌の疾患特異的尺度として、本邦ではQOL-ACDが使用されることが多い。今回われわれは、QOL-ACDを用いた乳癌術前化学療法(neoadjuvant chemotherapy:NAC)後の予後解析を行った。対象は乳癌NAC症例228例とし、QOL-ACDを用いて後方視的に抗腫瘍効果や予後との相関について検討した。高QOL-ACD群208例(91.2%)は、低QOL-ACD群20例(8.8%)と比較して、NAC後の無病生存期間(p=0.009、logrank)および全生存期間(p=0.040、logrank)の延長を認めた。さらにNAC後は、NAC前と比較して包括的評価スコアの低下を認めるものの、抗腫瘍効果との相関を認めなかった。下位評価尺度において、病理学的完全奏効(pathological complete response:pCR)症例は、non-pCR症例と比較して、「医療に対する満足感と病気に対するコーピング」尺度の変化が低い結果であったが、「身体症状・疼痛」尺度では差は認められなかった。乳癌NAC症例において、QOL-ACDはNAC後の予

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/annonc/mdx697.018

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/annonc/mdx597

PubMed

Publishing type：Research paper (scientific journal)  

2007年5月〜2014年4月に乳腺・内分泌科で周術期化学療法としてFEC100療法、AC療法、TC療法を外来で行った乳癌患者中、事前処方の抗菌薬がない患者または400mg/日のモキシフロキサシン塩酸塩(MFLX)が3日分事前処方された患者を対象に、乳癌周術期療法中の発熱性好中球減少症(FN)に対するMFLX事前処方の有用性について検討した。対象期間中にFEC 100療法、AC療法、TC療法を施行した患者中、事前処方の抗菌薬がない患者またはMFLX事前処方患者は240名であった。除外を除き、事前処方なし74名、MFLX事前処方164名となった。MFLXの事前処方はFN治療のため有用な治療戦略と考えられた。

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Background/Aim: Recently, reports of the clinical implications of tumor-infiltrating lymphocytes (TILs) in breast cancer treatment have increased. We evaluated that chemotherapy with a TPD regimen (trastuzumab, pertuzumab, docetaxel) against HER2-positive breast cancer, using TILs as indicators. Patients and Methods: The subjects were 24 patients who had received TPD-chemotherapy. A semi-quantitative evaluation of lymphocytes invading the stroma in needle biopsy specimens prior to treatment as TILs was conducted, after which, sensitivity to chemotherapy and patient prognosis were evaluated. Results: Overall response rate was significantly higher in the high-TILs group than in the low-TILs group. Significant extension of the progression-free survival (PFS) and overall survival was found in the high-TILs group compared to the low-TILs group. In addition, high TILs numbers significantly contributed to the extension of PFS. Conclusion: Monitoring antitumor immune response using TILs might be a useful indicator for predicting the curative effects of TPD chemotherapy for HER2-positive breast cancer.

DOI： 10.21873/anticanres.11997

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

2007年5月〜2014年4月に乳腺・内分泌科で周術期化学療法としてFEC100療法、AC療法、TC療法を外来で行った乳癌患者中、事前処方の抗菌薬がない患者または400mg/日のモキシフロキサシン塩酸塩(MFLX)が3日分事前処方された患者を対象に、乳癌周術期療法中の発熱性好中球減少症(FN)に対するMFLX事前処方の有用性について検討した。対象期間中にFEC 100療法、AC療法、TC療法を施行した患者中、事前処方の抗菌薬がない患者またはMFLX事前処方患者は240名であった。除外を除き、事前処方なし74名、MFLX事前処方164名となった。MFLXの事前処方はFN治療のため有用な治療戦略と考えられた。

Publishing type：Research paper (scientific journal)  

Background: Phyllodes tumor is a rare breast mass. Most phyllodes tumors are benign, but occasionally some show malignancy. Even if the tumors are benign, they can easily show recurrence. Case presentation: We report a case of a 48-year-old Asian woman, who had previously undergone a tumorectomy of her left breast 12 years before, with a pathological diagnosis of fibroadenoma. Five years after the initial tumorectomy, the patient presented with an abnormally enlarged left breast. A biopsy determined the growth to be a phyllodes tumor
subsequently, a partial mastectomy was conducted. However, the patient's left breast showed rapid enlargement in the next 5 months. The treating physicians suspected a relapse and subsequently consulted with our hospital. The breast mass was resected at our institution. After this surgery, the patient had repeated episodes of relapse and underwent four additional operations. Since then, the patient has not had any additional relapse so far. Conclusions: We present a case of a phyllodes tumor with multiple episodes of relapse. Although phyllodes tumors commonly show relapse, this case was unique because of the number of episodes of relapse. This case highlights the need to carry out tumorectomy with adequate margins with subsequent careful observation to check for relapse.

DOI： 10.1186/s13256-017-1432-y

PubMed

Publishing type：Research paper (scientific journal)  

Background: Adrenocoricotrophic hormone (ACTH) -independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is a rare cause of Cushing's syndrome, and is characterized by bilateral adrenal hyperplasia. However, Primary aldosteronism (PA) is a relatively common adrenal disease.
Case presentation: A 56-year-old man who has been treated hypertension and diabetes mellitus was detected low plasma potassium level with an elevated level of plasma aldosterone concentration and bilateral adrenal swelling. Endocrinological examinations showed autonomous secretion of cortisol and aldosterone, with suppression of plasma ACTH level and renin activity. A selective adrenal venous sampling demonstrated that left adrenal gland was responsible for aldosterone hypersecretion. He was diagnosed preclinical Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular hyperplasia (AIMAH) associated with aldosterone producing adenoma of the left adrenal gland. A laparoscopic left adrenalectomy was performed.
Conclusion: The resected adrenal specimen histologically consisted with a diagnosis of AIMAH. Moreover, tiny cell clusters positive immunostaining for aldosterone synthase was revealed. This is a rare case of AIMAH accompanied by preclinical Cushing's syndrome and primary aldosteronism.

DOI： 10.1186/s12893-017-0293-z

PubMed

Publishing type：Research paper (scientific journal)  

神経節細胞腫は交感神経節細胞から発生し,交感神経系腫瘍のうち最も高分化な良性腫瘍である.臨床症状が乏しく,増大してから発見されることが多い腫瘍であるが,偶発副腎腫瘍として発見される頻度が増加している.症例は47歳の女性.偶然に最大径4cmの右副腎腫瘍を指摘された.内分泌学的には異常は認められず,画像的にも悪性腫瘍は否定的で,非機能性右副腎腫瘍の診断となった.手術適応としては境界型であるが,確定診断のため摘出術を施行した.腫瘤は被膜に覆われ,明らかな浸潤性の増殖は認められなかった.病理所見でも周囲組織への浸潤は認めなかった.腫瘍細胞は紡錘形で異型に乏しく,神経節細胞腫と診断された.非機能性偶発性副腎腫瘍の術前診断は困難な場合もあり,最大径が4cmを超えている場合や画像上非特異的な像を示す場合などには,診断と治療を兼ねた腹腔鏡下副腎摘除術を選択することも許容されると考えられた.(著者抄録)

Publishing type：Research paper (scientific journal)  

神経節細胞腫は交感神経節細胞から発生し,交感神経系腫瘍のうち最も高分化な良性腫瘍である.臨床症状が乏しく,増大してから発見されることが多い腫瘍であるが,偶発副腎腫瘍として発見される頻度が増加している.症例は47歳の女性.偶然に最大径4cmの右副腎腫瘍を指摘された.内分泌学的には異常は認められず,画像的にも悪性腫瘍は否定的で,非機能性右副腎腫瘍の診断となった.手術適応としては境界型であるが,確定診断のため摘出術を施行した.腫瘤は被膜に覆われ,明らかな浸潤性の増殖は認められなかった.病理所見でも周囲組織への浸潤は認めなかった.腫瘍細胞は紡錘形で異型に乏しく,神経節細胞腫と診断された.非機能性偶発性副腎腫瘍の術前診断は困難な場合もあり,最大径が4cmを超えている場合や画像上非特異的な像を示す場合などには,診断と治療を兼ねた腹腔鏡下副腎摘除術を選択することも許容されると考えられた.(著者抄録)

Publishing type：Research paper (scientific journal)  

Background: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of beta-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy.
Methods: The subjects included 52 patients with MBC who underwent chemotherapy with eribulin. The expression levels of Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER) 2, Ki67, beta-tubulin class III, GSTP-1 and TLE-3 were evaluated using immunostaining employing needle biopsy specimens.
Results: Patients with TLE3-negative tumors displayed significantly poorer outcomes regarding progression-free survival than patients with TLE3- positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed (p = 0.011, log-rank). In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients (p = 0.433, log-rank) or of patients with non-TNBC lesions (p = 0.659, log-rank). Based on a univariate analysis of 22 TNBC cases, a better progression-free survival correlated significantly with a positive TLE3 expression in the tumor (p = 0.025). A multivariate logistic regression analysis including 22 patients with TNBC also showed that a positive TLE3 expression significantly correlated with a better progression-free survival (p = 0.037).
Conclusions: Our findings suggest that TLE3 is a useful marker for predicting the therapeutic effect of eribulin chemotherapy for TNBC.

DOI： 10.1186/s12885-017-3598-5

PubMed

DOI： 10.1158/1538-7445.AM2017-3179

DOI： 10.1158/1538-7445.AM2017-2351

DOI： 10.1158/1538-7445.AM2017-2343

Publishing type：Research paper (scientific journal)  

61歳女性。右乳房の同一腫瘤内に非浸潤性小葉癌(LCIS)および浸潤性乳管癌の混在を認めた乳腺超音波検査、CT検査およびMRI検査所見により右乳癌cT1N0M0 cStage I、Luminal A likeと診断し、乳腺円状部分切除およびセンチネルリンパ生検を施行した。リンパ節への転移が認められたため、腋窩リンパ節郭清術を追加した。病理診断では、腫瘍細胞が間質浸潤する硬癌と線管形成を示す乳頭腺管癌が混在していたが、硬癌が優勢であった。また、同部位の乳頭側にLCISを認めた。術後は残存乳腺への外照射を施行し、アナストロゾールで内分泌療法を行った。術後2年で再発を認めていない。

CiNii Article

Publishing type：Research paper (scientific journal)  

61歳女性。右乳房の同一腫瘤内に非浸潤性小葉癌(LCIS)および浸潤性乳管癌の混在を認めた乳腺超音波検査、CT検査およびMRI検査所見により右乳癌cT1N0M0 cStage I、Luminal A likeと診断し、乳腺円状部分切除およびセンチネルリンパ生検を施行した。リンパ節への転移が認められたため、腋窩リンパ節郭清術を追加した。病理診断では、腫瘍細胞が間質浸潤する硬癌と線管形成を示す乳頭腺管癌が混在していたが、硬癌が優勢であった。また、同部位の乳頭側にLCISを認めた。術後は残存乳腺への外照射を施行し、アナストロゾールで内分泌療法を行った。術後2年で再発を認めていない。

Publishing type：Research paper (scientific journal)  

61歳女性。右乳房の同一腫瘤内に非浸潤性小葉癌(LCIS)および浸潤性乳管癌の混在を認めた乳腺超音波検査、CT検査およびMRI検査所見により右乳癌cT1N0M0 cStage I、Luminal A likeと診断し、乳腺円状部分切除およびセンチネルリンパ生検を施行した。リンパ節への転移が認められたため、腋窩リンパ節郭清術を追加した。病理診断では、腫瘍細胞が間質浸潤する硬癌と線管形成を示す乳頭腺管癌が混在していたが、硬癌が優勢であった。また、同部位の乳頭側にLCISを認めた。術後は残存乳腺への外照射を施行し、アナストロゾールで内分泌療法を行った。術後2年で再発を認めていない。

CiNii Article

Publishing type：Research paper (scientific journal)  

Background: Kimura's disease (KD; eosinophilic granuloma of soft tissue) is an inflammatory granulomatous disorder of unknown cause with eosinophilic infiltration that occurs mainly in soft tissue. KD occurs mainly in the head and neck, but development in the axillary region is very rare.
Case presentation: A 74-year-old Japanese woman was evaluated for a mass that she noted in the left axillary region. On physical examination, there was a palpable, thumb-sized, hard, elastic, freely movable mass in the left axilla. Blood tests showed elevated soluble interleukin-2 receptor (sIL-2R), normal serum immunoglobulin (Ig) G4, and elevated serum IgE. Ultrasonography of the left axilla showed multiple lymph nodes (LNs) with irregular margins in which central hyperechogenicity was lost. A systemic search by computed tomography (CT) showed no systemic lymphadenopathy or other mass-like lesions suspicious for a primary tumour other than in the left axillary LNs. Biopsy of an excised LN was performed under local anaesthesia for a definitive diagnosis. Histopathology showed various-sized lymphoid follicles, large nodular lesions with an enlarged mantle zone, multiple various-sized germinal centres in single nodules, and eosinophilic infiltration between the nodes. Immunohistochemical (IHC) staining of the germinal centres was positive for cluster of differentiation (CD) 10, positive for B-cell lymphoma (bcl)-6, and negative for bcl-2. These findings led to a diagnosis of KD. Ultrasound after 3 months of follow-up showed disappearance of the axillary lymphadenopathy.
Conclusions: A very rare case of KD in the axillary LNs was described. KD has the potential to occur in any region.

DOI： 10.1186/s12893-017-0260-8

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Circulating tumor cells (CTCs) are linked to metastatic relapse and are regarded as a prognostic marker for human cancer. High expression of plakoglobin, a cell adhesion protein, within the primary tumor is positively associated with CTC clusters in breast cancer. In this study, we investigated the correlation between plakoglobin expression and survival of breast cancer. METHODS: We evaluated 121 breast cancer patients treated with neoadjuvant chemotherapy. Expression of plakoglobin was identified by immunohistochemical staining in the cell membrane. We also examined the relation between the expression of plakoglobin and E-cadherin, an epithelial-mesenchymal transition (EMT) marker. RESULTS: Patients with high plakoglobin expression had significantly worse distant-metastasis-free survival (DMFS) (P = 0.016, log rank). Plakoglobin expression had no correlation with pathological complete response rate (P = 0.627). On univariate analysis with respect to distant metastasis, high plakoglobin expression showed worse prognosis than low plakoglobin expression [P = 0.036, hazard ratio (HR) = 3.719]. Multivariate analysis found the same result (P = 0.013, HR = 5.052). In addition, there was a significant relationship between the expression of plakoglobin and E-cadherin (P = 0.023). CONCLUSIONS: Plakoglobin expression is an independent prognostic factor in patients with breast cancer, particularly for DMFS, and this is related to EMT.

DOI： 10.1186/s40364-017-0099-2

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.3892/mco.2017.1176

PubMed

Publishing type：Research paper (scientific journal)  

症例1は73歳女性で、半年前より左乳房腫瘤を触知するも放置していた。左乳頭直下に約7cm大の弾性硬の腫瘤を触知した。針生検で間質肉腫が強く疑われ、単純乳房切除術を施行した。術後補助療法は施行せず、10ヵ月無再生存中である。症例2は41歳女性で、右乳房痛にて近医を受診、乳輪下膿瘍が疑われたため紹介となった。針生検による病理診断の結果、間質肉腫が疑われたため、単純乳房切除術を施行した。術後補助療法は施行せず、1年6ヵ月無再発生存中である。2例とも間質内に短紡錘形の細胞が密に増殖しており、免疫組織染色にてサイトケラチン抗原など上皮性マーカーの発現がないことを確認し、除外診断的に間質肉腫との病理診断に至った。

Publishing type：Research paper (scientific journal)  

症例1は73歳女性で、半年前より左乳房腫瘤を触知するも放置していた。左乳頭直下に約7cm大の弾性硬の腫瘤を触知した。針生検で間質肉腫が強く疑われ、単純乳房切除術を施行した。術後補助療法は施行せず、10ヵ月無再生存中である。症例2は41歳女性で、右乳房痛にて近医を受診、乳輪下膿瘍が疑われたため紹介となった。針生検による病理診断の結果、間質肉腫が疑われたため、単純乳房切除術を施行した。術後補助療法は施行せず、1年6ヵ月無再発生存中である。2例とも間質内に短紡錘形の細胞が密に増殖しており、免疫組織染色にてサイトケラチン抗原など上皮性マーカーの発現がないことを確認し、除外診断的に間質肉腫との病理診断に至った。

CiNii Article

Publishing type：Research paper (scientific journal)  

Background
Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.
Methods
TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.
Results
Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).
Conclusion
The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

DOI： 10.1371/journal.pone.0170634

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.SABCS16-P3-04-20

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.SABCS16-P2-05-05

Publishing type：Research paper (scientific journal)  

Background: Tonsillar metastasis is very rare and accounts for only 0.8% of tonsillar tumors. And phyllodes tumor of the breast with tonsillar metastasis is very rare. Case presentation: A 57-year-old Japanese woman received surgery (partial mastectomy) of malignant phyllodes tumor. Seven months after initial surgery, pharyngeal pain, swelling, and a feeling of dyspnea developed, and tumor was found in the left palatine tonsil. Computed tomography for further evaluation showed a tonsillar lesion with contrast enhancement, and tonsillar metastasis was suspected. The metastatic lung tumors had not progressed. Laryngoscopic biopsy showed a tonsillar metastasis from the malignant phyllodes tumor. Despite the diagnosis of malignant phyllodes tumor with tonsillar and pulmonary metastases, the patient refused further treatment and died about 1 month later. Conclusions: A patient with a malignant phyllodes tumor of the breast and tonsillar metastasis was reported, along with a discussion of the relevant literature of this very rare pattern of metastasis.

DOI： 10.1186/s13104-017-2375-5

PubMed

Publishing type：Research paper (scientific journal)  

Background: Triple-negative breast cancer (TNBC) has a poor prognosis because of frequent recurrence. Androgen receptor (AR) is involved in the pathogenesis of breast cancer, but its role is not clearly defined. The aim of this study was to explore the expression of AR and its relationship with clinicopathologic features in TNBC. Methods: This study investigated 1036 cases of sporadic invasive breast carcinoma. Immunohistochemical assays were performed to determine the expression of AR in 190 TNBC samples. The relationships between AR expression and clinicopathologic data and prognosis were analyzed. Results: In 190 TNBC cases, the prognosis of AR-positive patients was significantly better (p = 0.019, log-rank) than AR-negative patients, and in multivariate analysis, AR expression was an independent indicator of good prognosis (p = 0.039, hazard ratio = 0.36). In patients with disease relapse, AR positivity was significantly correlated with better prognosis (p = 0.034, log-rank). Conclusions: AR expression may be useful as a subclassification marker for prognosis in TNBC.

DOI： 10.3390/cancers9010004

PubMed

Publishing type：Research paper (scientific journal)  

Ganglioneuroma is a benign well differentiated neural tumor, and arises from ganglion cells of the sympathetic nerve. It lacks clinical symptoms and has often enlarged when it is detected. The tumor has increasingly been found as an adrenal incidentaloma. We, herein, report a case of ganglioneuroma of the right adrenal gland. A 47-year-old woman was referred to our hospital for an incidentally found right adrenal tumor of 45 mm in maximum diameter. No abnormalities in the endocrine function or images suggestive of malignancy were found. Right nonfunctioning adrenal tumor was considered. Laparoscopic right adrenalectomy conducted to make the definite diagnosis revealed that the tumor was a ganglioneuroma of the adrenal gland consisted of spindle shaped tumor cells and nests of ganglion cells without atypia. Diagnostic and therapeutic laparoscopic adrenalectomy could feasibly be considered for relatively large (>4 cm in maximum diameter) adrenal tumors with non-typical imaging features.

DOI： 10.3919/jjsa.78.2135

CiNii Article

Publishing type：Research paper (scientific journal)  

<p>Febrile neutropenia (FN) is an oncologic emergency requiring immediate treatment. Outpatients who develop a fever are often instructed to take previously prescribed oral antibiotics without any initial assessment. Oral moxifloxacin hydrochloride (MFLX) is efficacious and safe in low-risk febrile neutropenic patients, but the use of MFLX according to the patients' discretion has not yet been established. In this study, we investigated the effectiveness and safety of the treatment technique during adjuvant or neoadjuvant chemotherapy for breast cancer. The 229 patients received 839 administrations of chemotherapy during the study period and 82 patients (35.8％) had a total of 128 febrile episodes (15.3％). The rate of visits due to heat generation in the pre-prescription group was significantly lower than that in the non pre-prescription group (33/99 [33.3％] vs 24/29 [82.8％], <i>P</i> < 0.001, by the episode). Our results suggest that the strategy might be an effective option for the management of FN of outpatients by reducing the number of hospital visits required.</p>

DOI： 10.5649/jjphcs.43.577

CiNii Article

Publishing type：Research paper (scientific journal)  

Anaplastic thyroid cancer (ATC) is a rare malignancy that progresses extremely aggressively and often results in dismal prognosis. We investigated the efficacy of inhibiting the activated RAS/RAF/MEK pathway in ATC cells aiming to clarify the mechanism of effect and resistance. Four human ATC cell lines (ACT-1, OCUT-2, OCUT-4 and OCUT-6) were used. OCUT-4 had a BRAF mutation. OCUT-2 had both BRAF and PI3KCA mutations. ACT-1 and OCUT-6 had wild type BRAF and NRAS mutations. The effects of dabrafenib, a selective inhibitor of the BRAFv 600E kinase, and trametinib, a reversible inhibitor of MEK activity, were investigated. Dabrafenib strongly inhibited the viability in BRAF mutated cells by demonstrating GO/G1-arrest via the downregulation of MEK/ERK phosphorylation. Upregulated phosphorylation of MEK was observed in RAS mutated cells after dabrafenib treatment and caused VEGF upregulation, but was not related to the cellular proliferation. Trametinib inhibited the cellular viability to variable degrees in every cell by downregulating ERK phosphorylation. Dual blockade by both inhibitors demonstrated clear cytostatic effect in all the cells. OCUT-4 showed the weakest sensitivity to trametinib, no additional effect of either inhibitor in combination with the other, and an increase of SNAI1 mRNA expression after treatment with inhibitors, suggesting a mechanism for resistance. Our findings demonstrated the efficacy of a mutation-selective BRAF inhibitor and a MEK inhibitor in human ATC cells in a genetic alteration specific manner.

DOI： 10.3892/ijo.2016.3723

PubMed

Publishing type：Research paper (scientific journal)  

癌宿主因子における炎症指標の有用性について検証した。グラスゴー予後予測スコアはCRP値とアルブミン値によって算出されるが、その他の指標はそれぞれの因子の絶対値の組み合わせで求められる。カットオフ値はROC解析で求めることが多く、評価項目は全生存期間または無病生存期間に関連して測定されることが多い。すべての指標において基準とされる数値は存在しない。末梢血から求められる炎症反応や栄養状態、免疫環境などの宿主因子は、有用な予後および治療効果予測因子である可能性が示唆された。

Publishing type：Research paper (scientific journal)  

癌宿主因子における炎症指標の有用性について検証した。グラスゴー予後予測スコアはCRP値とアルブミン値によって算出されるが、その他の指標はそれぞれの因子の絶対値の組み合わせで求められる。カットオフ値はROC解析で求めることが多く、評価項目は全生存期間または無病生存期間に関連して測定されることが多い。すべての指標において基準とされる数値は存在しない。末梢血から求められる炎症反応や栄養状態、免疫環境などの宿主因子は、有用な予後および治療効果予測因子である可能性が示唆された。

Publishing type：Research paper (scientific journal)  

癌宿主因子における炎症指標の有用性について検証した。グラスゴー予後予測スコアはCRP値とアルブミン値によって算出されるが、その他の指標はそれぞれの因子の絶対値の組み合わせで求められる。カットオフ値はROC解析で求めることが多く、評価項目は全生存期間または無病生存期間に関連して測定されることが多い。すべての指標において基準とされる数値は存在しない。末梢血から求められる炎症反応や栄養状態、免疫環境などの宿主因子は、有用な予後および治療効果予測因子である可能性が示唆された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 52-year-old woman visited our hospital with a chief complaint of a mass in the left breast. Palpation revealed a mass approximately 3 cm in diameter located on the outer aspect of the left breast. Breast ultrasound revealed a hypoechoic area with an indistinct border, which suggested breast cancer or mastitis. A needle biopsy revealed no evidence of malignancy, and granulomatous mastitis was diagnosed. Antibiotic therapy showed no improvement; therefore, we began prednisolone treatment for the patient. The mass diameter decreased over the subsequent 5 months after initiating this treatment, and we decreased the dose of prednisolone gradually. At present, when 8 months have elapsed after the diagnosis, the patient is doing well without any aggravation of signs or symptoms. The pathological findings of an inflammatory pseudotumor and granulomatous mastitis is similar, relatively rare benign diseases. As the inflammatory pseudotumor has clinical features resembling those of breast cancer, it is an important clinical entity.

PubMed

Publishing type：Research paper (scientific journal)  

葉状腫瘍は乳腺腫瘍のなかでまれであり、鑑別診断については針生検による少量の組織検体では困難であると考えられている。症例は70歳、女性。右乳房腫瘤を自覚し近医を受診し、精査加療目的にて当院紹介となった。乳腺超音波検査では、右乳腺B領域に最大径5.4cm大の辺縁平滑・境界明瞭な低エコー腫瘤が確認された。同部位の針生検にて、間質に多形な核を伴う紡錘形細胞の束状・びまん性の増殖を認め、紡錘細胞肉腫との診断であった。免疫組織染色では、CAM5.2陰性、AE1/AE3一部陽性、bcl-2陽性、ER陰性、PgR陰性、SMA陽性、S-100陰性、desmin陰性、CD34陰性、keratin 5/6陰性で葉状腫瘍が疑われた。確定診断目的にて乳腺腫瘤切除術を施行し、悪性葉状腫瘍との病理診断に至った。今回、紡錘細胞肉腫との鑑別が困難であった悪性葉状腫瘍の1例を経験した。確定診断には摘出生検による十分な組織診断も考慮すべきであり、文献的考察を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例は52歳、女性。左乳房腫瘤触知を主訴に来院した。触診では左乳房外側に約3cmの腫瘤を触知し、乳腺超音波検査では3.8×3.8×2.4cmの不整形低エコー領域を認めた。乳癌や乳腺炎を鑑別疾患とし針生検を施行したところ、肉芽腫性乳腺炎の診断であった。抗生剤投与で改善せず、prednisoloneの投与にて主病変の縮小を認めた。ここで確定診断目的に吸引式乳腺組織生検(EnCor ENSPIREシステム)を施行したところ、炎症性偽腫瘍との診断に至った。prednisolone投与5ヵ月後には約5mmにまで退縮したためprednisoloneを漸減したが、増悪を認めていない。炎症性偽腫瘍と肉芽腫性乳腺炎の病理所見は類似するが、ともに乳癌と似た臨床像を示すことがあり、臨床的に重要な乳腺疾患である。(著者抄録)

Publishing type：Research paper (scientific journal)  

葉状腫瘍は乳腺腫瘍のなかでまれであり、鑑別診断については針生検による少量の組織検体では困難であると考えられている。症例は70歳、女性。右乳房腫瘤を自覚し近医を受診し、精査加療目的にて当院紹介となった。乳腺超音波検査では、右乳腺B領域に最大径5.4cm大の辺縁平滑・境界明瞭な低エコー腫瘤が確認された。同部位の針生検にて、間質に多形な核を伴う紡錘形細胞の束状・びまん性の増殖を認め、紡錘細胞肉腫との診断であった。免疫組織染色では、CAM5.2陰性、AE1/AE3一部陽性、bcl-2陽性、ER陰性、PgR陰性、SMA陽性、S-100陰性、desmin陰性、CD34陰性、keratin 5/6陰性で葉状腫瘍が疑われた。確定診断目的にて乳腺腫瘤切除術を施行し、悪性葉状腫瘍との病理診断に至った。今回、紡錘細胞肉腫との鑑別が困難であった悪性葉状腫瘍の1例を経験した。確定診断には摘出生検による十分な組織診断も考慮すべきであり、文献的考察を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

進行再発乳癌における治療の目的は、全生存期間の延長と生活の質(QOL)の改善である。そのため、治療効果が高く有害事象が少ない薬剤が望まれる。症例は43歳、女性。右乳房腫瘤を自覚し近医を受診、精査加療目的にて当院紹介となった。乳腺超音波検査において右乳腺C領域に2.9cm大の低エコー腫瘤が確認され、針生検にて浸潤性乳管癌(ER90%、PgR陰性、HER2陰性、Ki-67中等度発現)との診断を得た。また、鎖骨上に転移を疑わせるリンパ節が認められたため、穿刺吸引細胞診を行ったところ悪性であった。治療前診断は右乳癌、cT2N3M0、stage IIIC、Luminal B likeとした。エリブリン化学療法を開始し、6 cycles終了後の画像検査にて右乳腺腫瘤は同定困難となり、鎖骨上リンパ節も消失したため手術を施行した。Grade 2以上の有害事象は認めなかった。摘出標本の病理学的診断では病理学的完全奏効(pathological complete response:pCR)(Grade 3)が確認された。今回われわれは、エリブリン化学療法によりpCRが得られた局所進行乳癌の1例を経験した。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A goal for treating advanced disease is prolonging survival while maintaining a good quality of life(QOL). Eribulin chemotherapy may be suitable for this purpose. We report a case of advanced breast cancer with pathological complete response (pCR)obtained by eribulin chemotherapy. The patient was a 43-year-old woman who complained of a right mammary mass. A tumor measuring approximately 3 cm was palpated, and breast cancer was detected via ultrasound examination. Core needle biopsy indicated invasive ductal carcinoma based on histopathological findings. A metastasis to the supraclavicular lymph node was observed and was found to be malignant via fine-needle aspiration cytology. The patient was diagnosed with advanced breast cancer cT2N3M0, stage III C, Luminal B like. She underwent primary systemic therapy with 6 cycles of eribulin. The patient exhibited a clinical complete response to eribulin chemotherapy. Thereafter, a right mastectomy with level 3 axillary lymph node dissection was performed. Pathological diagnosis of the surgical specimen was pCR. At present, 3 years after surgery, the patient has no recurrence.

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 70-year-old woman noticed a mass in her right breast. Breast ultrasonography showed a low echo mass with a smooth border to the greatest dimension measuring 5.4 cm. Needle biopsy showed an increase in the number of spindle-shaped cells with diffuse fascicles having nuclei with seasonal polymorphisms in the stroma, which led to the final diagnosis of spindle cell sarcoma. Immunohistochemistry analysis showed a CAM5.2-negative, AE1/AE3 partly-positive, bcl-2-positive, ER-negative, PgR-negative, SMA-positive, S-100-negative, desmin-negative, CD34-negative, and keratin 5/6-negative tumor that was suspected to be a phyllodes tumor. Differential diagnoses included sarcoma-likecance r, stromal sarcoma, and malignant phyllodes tumor. Breast mass resection was performed for a definitive diagnosis. The final pathological analysis showed a malignant phyllodes tumor. To date, we have encountered 1 case of malignant phyllodes tumor that was difficult to distinguish from a spindle cell sarcoma. Excisional biopsy is required for a definitive diagnosis.

PubMed

Publishing type：Research paper (scientific journal)  

症例は52歳、女性。左乳房腫瘤触知を主訴に来院した。触診では左乳房外側に約3cmの腫瘤を触知し、乳腺超音波検査では3.8×3.8×2.4cmの不整形低エコー領域を認めた。乳癌や乳腺炎を鑑別疾患とし針生検を施行したところ、肉芽腫性乳腺炎の診断であった。抗生剤投与で改善せず、prednisoloneの投与にて主病変の縮小を認めた。ここで確定診断目的に吸引式乳腺組織生検(EnCor ENSPIREシステム)を施行したところ、炎症性偽腫瘍との診断に至った。prednisolone投与5ヵ月後には約5mmにまで退縮したためprednisoloneを漸減したが、増悪を認めていない。炎症性偽腫瘍と肉芽腫性乳腺炎の病理所見は類似するが、ともに乳癌と似た臨床像を示すことがあり、臨床的に重要な乳腺疾患である。(著者抄録)

Publishing type：Research paper (scientific journal)  

進行再発乳癌における治療の目的は、全生存期間の延長と生活の質(QOL)の改善である。そのため、治療効果が高く有害事象が少ない薬剤が望まれる。症例は43歳、女性。右乳房腫瘤を自覚し近医を受診、精査加療目的にて当院紹介となった。乳腺超音波検査において右乳腺C領域に2.9cm大の低エコー腫瘤が確認され、針生検にて浸潤性乳管癌(ER90%、PgR陰性、HER2陰性、Ki-67中等度発現)との診断を得た。また、鎖骨上に転移を疑わせるリンパ節が認められたため、穿刺吸引細胞診を行ったところ悪性であった。治療前診断は右乳癌、cT2N3M0、stage IIIC、Luminal B likeとした。エリブリン化学療法を開始し、6 cycles終了後の画像検査にて右乳腺腫瘤は同定困難となり、鎖骨上リンパ節も消失したため手術を施行した。Grade 2以上の有害事象は認めなかった。摘出標本の病理学的診断では病理学的完全奏効(pathological complete response:pCR)(Grade 3)が確認された。今回われわれは、エリブリン化学療法によりpCRが得られ

Publishing type：Research paper (scientific journal)  

症例は52歳、女性。左乳房腫瘤触知を主訴に来院した。触診では左乳房外側に約3cmの腫瘤を触知し、乳腺超音波検査では3.8×3.8×2.4cmの不整形低エコー領域を認めた。乳癌や乳腺炎を鑑別疾患とし針生検を施行したところ、肉芽腫性乳腺炎の診断であった。抗生剤投与で改善せず、prednisoloneの投与にて主病変の縮小を認めた。ここで確定診断目的に吸引式乳腺組織生検(EnCor ENSPIREシステム)を施行したところ、炎症性偽腫瘍との診断に至った。prednisolone投与5ヵ月後には約5mmにまで退縮したためprednisoloneを漸減したが、増悪を認めていない。炎症性偽腫瘍と肉芽腫性乳腺炎の病理所見は類似するが、ともに乳癌と似た臨床像を示すことがあり、臨床的に重要な乳腺疾患である。(著者抄録)

Publishing type：Research paper (scientific journal)  

葉状腫瘍は乳腺腫瘍のなかでまれであり、鑑別診断については針生検による少量の組織検体では困難であると考えられている。症例は70歳、女性。右乳房腫瘤を自覚し近医を受診し、精査加療目的にて当院紹介となった。乳腺超音波検査では、右乳腺B領域に最大径5.4cm大の辺縁平滑・境界明瞭な低エコー腫瘤が確認された。同部位の針生検にて、間質に多形な核を伴う紡錘形細胞の束状・びまん性の増殖を認め、紡錘細胞肉腫との診断であった。免疫組織染色では、CAM5.2陰性、AE1/AE3一部陽性、bcl-2陽性、ER陰性、PgR陰性、SMA陽性、S-100陰性、desmin陰性、CD34陰性、keratin 5/6陰性で葉状腫瘍が疑われた。確定診断目的にて乳腺腫瘤切除術を施行し、悪性葉状腫瘍との病理診断に至った。今回、紡錘細胞肉腫との鑑別が困難であった悪性葉状腫瘍の1例を経験した。確定診断には摘出生検による十分な組織診断も考慮すべきであり、文献的考察を加えて報告する。(著者抄録)

Publishing type：Research paper (scientific journal)  

Background
The peripheral blood platelet-lymphocyte ratio (PLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer-bearing patients. While some reports suggest a correlation between PLR and prognosis, few studies have examined the relationship between PLR and sensitivity to chemotherapy. We conducted a study on whether PLR could serve as a predictor of the therapeutic effects of neoadjuvant chemotherapy (NAC).
Methods
PLR was evaluated in 177 breast cancer patients treated with the NAC 5-fluorouracil, epirubicin and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between PLR and prognosis, and between PLR and the efficacy of NAC, were evaluated retrospectively.
Results
The low PLR group had significantly more patients &gt; 56 years old (p = 0.001) and postmenopausal women (p = 0.001) than the high PLR group. The low PLR group also had a higher pathologic complete response (pCR) rate (p = 0.019). On examining the correlation with prognosis, the low-PLR group was found to have significantly longer disease-free survival (p = 0.004) and overall survival (p = 0.032) than the high PLR group. Multivariate analysis also revealed that lymph node metastasis (p = 0.043, hazard ratio = 4.40) and a high PLR (p = 0.005, hazard ratio = 2.84) were independent, unfavorable prognostic factors.
Conclusions
For patients with breast cancer treated with NAC, a low PLR indicated high chemotherapy sensitivity, suggesting that PLR could serve as a predictive marker of the therapeutic effect of NAC.

DOI： 10.1371/journal.pone.0153459

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.AM2016-5127

DOI： 10.1158/1538-7445.AM2016-3939

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.AM2016-1412

Publishing type：Research paper (scientific journal)  

Background: Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune response, and are important in predicting treatment responses and outcomes for various types of cancer. Recently, specific TIL subsets have been reported to be clinically useful in predicting treatment responses. The CD8+/FOXP3+ TIL ratio (CFR) may be a more sensitive indicator for monitoring immune function. This study investigated the clinical significance and value of CFR as a biomarker to predict treatment responses to neoadjuvant chemotherapy for breast cancer.
Methods: Patients with resectable early-stage breast cancer treated with neoadjuvant chemotherapy at Osaka City University Hospital, Japan, between 2007 and 2013 were included. Oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, Ki-67, CD8 and FOXP3 status were assessed by immunohistochemistry, and correlated with pathological complete response (pCR).
Results: A total of 177 patients were included, of whom 90 had a high CFR and 87 a low CFR. Triple-negative breast cancer (TNBC) was more common in the high-CFR group than in the low-CFR group (46 versus 23 per cent; P = 0.002), as was HER2-enriched breast cancer (HER2BC) (27 versus 14 per cent; P = 0.033). Among these patients, the pCR rate was significantly higher in the high-CFR group than in the low-CFR group (TNBC: P = 0.022; HER2BC: P &lt; 0.001). In multivariable analysis high-CFR status was an independent predictor of a favourable prognosis: hazard ratio 0.24 (95 per cent c.i. 0.05 to 0.72; P = 0.015) for TNBC and 0.10 (0.10 to 0.90; P = 0.041) for HER2BC.
Conclusion: The CFR may be a useful biomarker to predict treatment response to neoadjuvant therapy in aggressive breast cancer subtypes, such as TNBC and HER2BC.

DOI： 10.1002/bjs.10127

PubMed

Publishing type：Research paper (scientific journal)  

The neutrophil/lymphocyte ratio (NLR) has been reportedly associated with prognosis in cancer patients by influencing both cancer progression and chemosensitivity. However, the correlation between NLR and the outcome of neoadjuvant chemotherapy (NAC) in breast cancer patients remains unclear.
NLR was evaluated in 177 patients with breast cancer treated with NAC with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between NLR and prognosis, including the efficacy of NAC, was evaluated retrospectively.
NLR ranged from 0.5 to 10.6. Fifty-eight patients with low NLR (&lt; 3.0) had a higher pathological complete response (pCR) rate (p &lt; 0.001) and were more frequently diagnosed with ER-negative/progesterone receptor (PR)-negative/HER2-negative (triple-negative) breast cancer (TNBC; p &lt; 0.001) compared with patients with high NLR (a parts per thousand yen3.0). Among TNBC patients who achieved pCR, disease-free survival (p = 0.006) and overall survival (p &lt; 0.001) were significantly longer in patients with low NLR than in those with high NLR. Low NLR was associated with a significantly favorable prognosis in TNBC patients who achieved pCR, according to univariate analysis (p = 0.044, hazard ratio = 0.06).
Low NLR may indicate high efficacy and favorable outcome after NAC in patients with TNBC.

DOI： 10.1245/s10434-015-4934-0

PubMed

Publishing type：Research paper (scientific journal)  

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

DOI： 10.1186/s40064-016-1833-1

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1538-7445.SABCS15-P3-07-33