Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer 9869 EN Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Shinichiro Kubo Department of Breast and Thyroid Surgery, Fukuyama City Hospital Mari Yamamoto Department of Breast and Thyroid Surgery, Fukuyama City Hospital Tetsumasa Yamashita Department of Breast and Thyroid Surgery, Fukuyama City Hospital Chihiro Kuwahara Department of Breast and Thyroid Surgery, Fukuyama City Hospital Masahiko Ikeda Department of Breast and Thyroid Surgery, Fukuyama City Hospital Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/mu L for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 1 2024 Ectopic Breast Cancer Arising within an Axillary Lymph Node 89 93 EN Kei Toshima Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Midori Filiz Nishimura Department of Molecular Hematopathology, Graduate School of Health Sciences, Okayama University Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Shogo Nakamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Maya Uno Department of Breast and Endocrine Surgery, Okayama University Hospital Ryo Yoshioka Department of Breast and Endocrine Surgery, Okayama University Hospital Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Yuko Takahashi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tsuguo Iwatani Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyuki Yanai Department of Diagnostic Pathology, Okayama University Hospital Case Report 10.18926/AMO/66676 We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 23 2021 YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development 12809 EN Miwa Fujihara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tatsuaki Takeda Departments of Pharmacy, Okayama University Hospital Yidan Zhu Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tomoka Mamori Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Ryo Yoshioka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Maya Uno Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yoko Suzuki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yuko Abe Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Minami Hatono Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Mariko Kochi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Iwamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Naruto Taira Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hiroyoshi Doihara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 Differences in Attitudes and Practices of Cancer Pain Management between Medical Oncologists and Palliative Care Physicians 431 437 EN Toshiki Kunitomi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichirou Nasu Department of Internal Medicine, Okayama Saiseikai General Hospital Daisuke Minami Palliative Care Team, Okayama University Hospital Takayuki Iwamoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Nishie Palliative Care Team, Okayama University Hospital Shinya Saito Palliative Care Team, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junji Matsuoka Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62394 This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-0904 9 3 2021 Simultaneous hot and cold thyroid nodules: Which is malignant? 1810 1811 EN Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Ruiko Hayashi Department of Internal Medicine, Kosei General Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Physicians should be aware of the risk of malignancy in patients with toxic multinodular goiter. Radionuclide scan cannot be used to predict the malignant potential of thyroid nodules. A comprehensive evaluation of imaging studies is needed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma 401 406 EN Takahiro Tsukioki Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Yusuke Ohtani Department of Breast and Endocrine Surgery, Okayama University Hospital Miwa Fujihara Department of Breast and Endocrine Surgery, Okayama University Hospital Yoko Suzuki Department of Breast and Endocrine Surgery, Okayama University Hospital Yukiko Kajihara Department of Breast and Endocrine Surgery, Okayama University Hospital Minami Hatono Department of Breast and Endocrine Surgery, Okayama University Hospital Kengo Kawada Department of Breast and Endocrine Surgery, Okayama University Hospital Mariko Kochi Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Hirokuni Ikeda Department of Breast and Endocrine Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital Original Article 10.18926/AMO/60799 Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC. No potential conflict of interest relevant to this article was reported.

AME Acta Medica Okayama 2304-3865 9 3 2020 Biomarkers of neoadjuvant/adjuvant chemotherapy for breast cancer 27 EN Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Yukiko Kajiwara Department of Breast and Endocrine Surgery, Okayama University Hospital Yidan Zhu Department of Breast and Endocrine Surgery, Okayama University Hospital Shigemichi Iha Department of Breast Oncology, Miyake Ofuku Clinic The improvement of tumor biomarkers prepared for clinical use is a long process. A good biomarker should predict not only prognosis but also the response to therapies. In this review, we describe the biomarkers of neoadjuvant/adjuvant chemotherapy for breast cancer, considering different breast cancer subtypes. In hormone receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative breast cancers, various genomic markers highly associated with proliferation have been tested. Among them, only two genomic signatures, the 21-gene recurrence score and 70-gene signature, have been reported in prospective randomized clinical trials and met the primary endpoint. However, these genomic markers did not suffice in HER2-positive and triple-negative (TN) breast cancers, which present only classical clinical and pathological information (tumor size, nodal or distant metastatic status) for decision making in the adjuvant setting in daily clinic. Recently, patients with residual invasive cancer after neoadjuvant chemotherapy are at a high-risk of recurrence for metastasis, which, in turn, make these patients best applicants for clinical trials. Two clinical trials have shown improved outcomes with post-operative capecitabine and ado-trastuzumab emtansine treatment in patients with either TN or HER2-positive breast cancer, respectively, who had residual disease after neoadjuvant chemotherapy. Furthermore, tumor-infiltrating lymphocytes (TILs) have been reported to have a predictive value for prognosis and response to chemotherapy from the retrospective analyses. So far, TILs have to not be used to either withhold or prescribe chemotherapy based on the absence of standardized evaluation guidelines and confirmed information. To overcome the low reproducibility of evaluations of TILs, gene signatures or digital image analysis and machine learning algorithms with artificial intelligence may be useful for standardization of assessment for TILs in the future. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0344-5704 86 1 2020 Influences of preoperative metformin on immunological factors in early breast cancer 55 63 EN Takahiro Tsukioki Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadahiko Shien Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Yoko Suzuki Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yukiko Kajihara Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Minami Hatono Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kengo Kawada Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mariko Kochi Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takayuki Iwamoto Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirokuni Ikeda Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naruto Taira Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroyoshi Doihara Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Toyooka Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Purpose</br> Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer.</br> Method</br> We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen.</br> Result</br> There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08).</br> Conclusion</br> Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0167-6806 182 2 2020 NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy 325 332 EN Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Fumikata Hara Breast Medical Oncology Department, Cancer Institute Hospital of JFCR Yukari Uemura Department of Clinical Research, National Center for Global Health and Medicine Hirofumi Mukai Department of Breast and Medical Oncology, National Cancer Center Hospital Toru Watanabe Department of Medical Oncology, Hamamatsu Oncology Center Yasuo Ohashi Department of Integrated Science and Engineering for Sustainable Society, Chuo University Background</br> Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer.</br> Methods</br> We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer</br> Results</br> Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients.</br> Conclusion</br> Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 13406868 27 5 2020 The efficacy of sequential second-line endocrine therapies (ETs) in postmenopausal estrogen receptor-positive and HER2-negative metastatic breast cancer patients with lower sensitivity to initial ETs 973 981 EN Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Tomomi Fujisawa Department of Breast Oncology, Gunma Prefectural Cancer Center Tadahiko Shien Okayama University Hospital Kazuhiro Araki Department of Medical Oncology, Gunma Prefectural Cancer Center Kentaro Sakamaki Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo Takafumi Sangai Department of Breast and Thyroid Surgery, Chiba University Hospital Yuichiro Kikawa Department of Breast Surgery, Kobe City Medical Center General Hospital Shintaro Takao Department of Breast Surgery, Hyogo Cancer Center Reiki Nishimura Department of Breast Oncology, Kumamoto Shinto General Hospital Masato Takahashi Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center Tomohiko Aihara Breast Center, Aihara Hospital Hirofumi Mukai Division of Breast and Medical Oncology, National Cancer Center Hospital East Naruto aira Department of Breast and Endocrine Surgery, Okayama University Hospital, Purpose</br> Second-line endocrine therapy (ET) for estrogen receptor (ER)-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) is offered based on the response to first-line ET. However, no clinical trials have evaluated the efficacy and safety of secondary ETs in patients with poor responses to initial ET. This study evaluated the efficacy of second-line ET in ER-positive and HER2-negative postmenopausal MBC patients with low or very low sensitivity to initial ET.</br> Methods</br> This multicenter prospective observational cohort study evaluated the response of 49 patients to second-line ETs in postmenopausal MBC patients with low or very low sensitivity to initial ET. The primary endpoint was the clinical benefit rate (CBR) for 24 weeks.</br> Results</br> Of the 49 patients assessed, 40 (82%) received fulvestrant in the second line, 5 (10%) received selective estrogen receptor modulators, 3 (6%) received aromatase inhibitors (AIs) alone, and 1 received everolimus with a steroidal AI. The overall CBR was 44.9% [90% confidence interval (CI): 34.6–57.6, p = 0.009]; CBR demonstrated similar significance across the progesterone receptor-positive (n = 39, 51.3%, 90% CI: 39.6–65.2, p = 0.002), very low sensitivity (n = 17, 58.8%, 90% CI: 42.0–78.8, p = 0.003), and non-visceral metastases (n = 25, 48.0%, 90% CI: 34.1–65.9, p = 0.018) groups. The median progression-free survival was 7.1 months (95% CI: 5.6–10.6).</br> Conclusion</br> Second-line ET might be a viable treatment option for postmenopausal patients with MBC with low and very low sensitivity to initial ET. Future studies based on larger and independent cohorts are needed to validate these findings. No potential conflict of interest relevant to this article was reported.

SpringerOpen Acta Medica Okayama 2198-7793 6 1 2020 Recurring radiation-induced angiosarcoma of the breast that was treated with paclitaxel chemotherapy: a case report 25 EN Yoko Suzuki Department of Breast and Endocrine surgery in Okayama University Japan Hospital Kohei Taniguchi Department of Pathological diagnosis, Okayama University Japan Hospital Minami Hatono Department of Breast and Endocrine surgery in Okayama University Japan Hospital Yukiko Kajiwara Department of Breast and Endocrine surgery in Okayama University Japan Hospital Yuko Abe Department of Breast and Endocrine surgery in Okayama University Japan Hospital Kengo Kawada Department of Breast and Endocrine surgery in Okayama University Japan Hospital Takahiro Tsukioki Department of Breast and Endocrine surgery in Okayama University Japan Hospital Mariko Kochi Department of Breast and Endocrine surgery in Okayama University Japan Hospital Keiko Nishiyama Department of Breast and Endocrine surgery in Okayama University Japan Hospital Takayuki Iwamoto Department of Breast and Endocrine surgery in Okayama University Japan Hospital Hirokuni Ikeda Department of Breast and Endocrine surgery in Okayama University Japan Hospital Tadahiko Shien Department of Breast and Endocrine surgery in Okayama University Japan Hospital Naruto Taira Department of Breast and Endocrine surgery in Okayama University Japan Hospital Masahiro Tabata Department of Hematology, Oncology, Respiratory, and Allergy Medicine, Okayama University Japan Hospital Hiroyuki Yanai Department of Pathological diagnosis, Okayama University Japan Hospital Hiroyoshi Doihara Department of Breast and Endocrine surgery in Okayama University Japan Hospital Background Angiosarcoma of the breast is very rare and can be divided into primary and secondary angiosarcoma. Radiation-induced angiosarcoma (RIAS) is classified as secondary angiosarcoma. Diagnosis of RIAS is difficult due to its rarity, and the interpretation of pathological imaging is complicated. In the National Comprehensive Care Network (NCCN) guidelines, the first choice of treatment is surgery with negative margins. Adjuvant radiotherapy (RT) for close soft tissue margins should be considered. Preoperative or adjuvant chemotherapy of nonmetastatic disease is not recommended for angiosarcoma. We report a case of RIAS, which was impossible to diagnose with core needle biopsy (CNB) but was diagnosed by excisional biopsy. The patient was then administered adjuvant chemotherapy using conjugated paclitaxel (PTX). <br/> Case presentation A 62-year-old woman noticed a tumor in her right breast. She had a history of right breast cancer and had undergone breast-conserving surgery, RT, and tamoxifen therapy 8 years previously. CNB, which was performed twice, was inconclusive. The tumor was surgically excised and pathological analysis yielded a diagnosis of angiosarcoma. She then underwent a right mastectomy. One month after she underwent right mastectomy, a nodule reappeared on the skin of her right breast, and excisional biopsy revealed recurrence of angiosarcoma. A few weeks later another nodule reappeared near the post-operative scar and excisional biopsy revealed recurrence of angiosarcoma. We assumed that surgical therapy was insufficient because the patient experienced relapse of angiosarcoma after complete mastectomy. After the second recurrence, we treated her with systemic chemotherapy using PTX. There was no evidence of recurrence 8 months after chemotherapy. <br/> Conclusion Although angiosarcoma is difficult to diagnose, many patients have a poor prognosis. Therefore, prompt treatment intervention is desired. Moreover, there is little evidence regarding adjuvant therapy of angiosarcoma since it is a rare disease. We consider that adjuvant therapy helped to effectively prevent recurrence in the patient after complete excision. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1526-8209 20 2 2020 Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer 117 124 EN Yuko Takahashi Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Iwamoto Departments of Breast and Endocrine Surgery, Okayama University Hospital Yoko Suzuki Departments of Breast and Endocrine Surgery, Okayama University Hospital Yukiko Kajiwara Departments of Breast and Endocrine Surgery, Okayama University Hospital Minami Hatono Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Tsukioki Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Kengo Kawada Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Mariko Kochi Departments of Breast and Endocrine Surgery, Okayama University Hospital Hirokuni Ikeda Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Naruto Taira Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Junji Matsuoka Departments of Palliative and Supportive Medicine, Okayama University Hospital Hiroyoshi Doihara Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Introduction</br> Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy.</br> Patients and Methods</br> We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III.</br> Results</br> Among hormone receptor–positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node–positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II.</br> Conclusion</br> In hormone receptor–positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials. No potential conflict of interest relevant to this article was reported.

Japanese Breast Cancer Society Acta Medica Okayama 1340-6868 24 2 2017 Development of a Japanese version of the BREAST-Q and the traditional psychometric test of the mastectomy module for the assessment of HRQOL and patient satisfaction following breast surgery 288 298 EN Miho Saiga Department of Plastic and Reconstructive Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrine Surgery, Okayama University Hospital Yoshihiro Kimata Satoko Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Yuko Mukai Department of Plastic and Reconstructive Surgery, Okayama University Hospital Kojiro Shimozuma Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University Taeko Mizoo Department of Breast and Endocrine Surgery, Okayama University Hospital Tomohiro Nogami Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrine Surgery, Okayama University Hospital Takayuki Motoki Department of Breast and Endocrine Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrine Surgery, Okayama University Hospital Junji Matsuoka Department of Breast and Endocrine Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrine Surgery, Okayama University Hospital BACKGROUND:　 An understanding of health-related quality of life (HRQOL) is of utmost importance in both oncological and esthetic breast surgery. The BREAST-Q is a patient-reported outcome (PRO) measure that investigates HRQOL and patient satisfaction before and after breast surgery. The aim of this study was to develop a Japanese version of the BREAST-Q including the mastectomy module, the reconstruction module, the augmentation module and the reduction/mastopexy module, and to assess the psychometric properties of the mastectomy module among Japanese women.　 METHODS:　 The Japanese version of the BREAST-Q was developed through forward translation, backward translation and patient testing. Traditional psychometric testing of the mastectomy module was administered to 45 post-mastectomy patients.　 RESULTS:　 The mastectomy, reconstruction, augmentation and reduction/mastopexy modules were formally developed into Japanese. Despite cultural difference between Japanese women and original target population, the contents were considered to be valid among Japanese woman. With the exception of the sexual well-being subscale, good reliability and validity were evident for the mastectomy module (Test-retest reliability 0.76-0.95, Chronbach's alpha coefficient 0.77-0.98).　 CONCLUSIONS:　 The BREAST-Q Japanese version is a useful PRO measure for investigating the impact of breast surgery on HRQOL and patient satisfaction. Further validation in younger Japanese women is needed to determine the usefulness of the sexual well-being subscale. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 5 2016 A Phase I Trial of 100mg/m2 Docetaxel in Patients with Advanced or Recurrent Breast Cancer 425 427 EN Tomoki Tamura Department of Allergy and Respiratory Medicine, Okayama University Hospital Taizo Hirata Department of Medical Oncology, National Hospital Organization Kure Medical Center Masahiro Tabata Department of Allergy and Respiratory Medicine, Okayama University Hospital Shiro Hinotsu Center for Innovative Clinical Medicine, Okayama University Hospital Akinobu Hamada Division of Clinical Pharmacology & Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Takayuki Motoki Department of Breast and Endocrinological Surgery, Okayama University Hospital Takayuki Iwamoto Department of Breast and Endocrinological Surgery, Okayama University Hospital Taeko Mizoo Department of Breast and Endocrinological Surgery, Okayama University Hospital Tomohiro Nogami Department of Breast and Endocrinological Surgery, Okayama University Hospital Tadahiko Shien Department of Breast and Endocrinological Surgery, Okayama University Hospital Naruto Taira Department of Breast and Endocrinological Surgery, Okayama University Hospital Junji Matsuoka Department of Breast and Endocrinological Surgery, Okayama University Hospital Hiroyoshi Doihara Department of Breast and Endocrinological Surgery, Okayama University Hospital Clinical Study Protocols 10.18926/AMO/54607 Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2. However, the approved dose in Japan is up to 75 mg/m2. We have launched a phase I trial evaluating 100 mg/m2 docetaxel in patients with advanced or relapsed breast cancer. The major eligibility criteria are as follows: age &ge;20 years, pathologically diagnosed breast cancer, recurrent or advanced breast cancer, a good performance status, and HER2 [human epidermal growth factor receptor 2] negative. The primary endpoint is demonstrated safety of 100 mg/m2 docetaxel. This study will clarify whether 100mg/m2 docetaxel can be administrated safely in Japanese patients with advanced or recurrent breast cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 6 2015 Correlation between 18F-fluorodeoxyglucose Positron Emission Tomography/computed Tomography and Clinicopathological Features in Invasive Ductal Carcinoma of the Breast 333 338 EN Maiko Ito Tadahiko Shien Mitsumasa Kaji Taeko Mizoo Takayuki Iwamoto Tomohiro Nogami Takayuki Motoki Naruto Taira Hiroyoshi Doihara Shinichiro Miyoshi Original Article 10.18926/AMO/53907 We evaluated the usefulness of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) examinations to predict the pathological features in primary breast cancer. In particular, we evaluated the correlation between the maximum standardized uptake values (SUVmax) obtained by 18F-FDG PET/CT and the Ki67 expression in estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). Primary IDC patients operated between March 2009 and July 2013 at Okayama University Hospital were enrolled. We evaluated the correlations between the SUVmax and age, postoperative pT, histological grade, lymph vascular invasion, status of hormone receptor, human epidermal growth factor receptor 2 (HER2), Ki67 expression and node status. The Ki67 expression was classified as high (>14%) versus low (<14%). We enrolled 138 patients with IDC. Their median SUVmax was 3.85 (range:0-52.57). In a univariate analysis, the SUVmax was significantly related to age, pT, histological grade, lymphovascular invasion, hormone receptor status, HER2 status, node status and Ki67. In the 113 patients with ER-positive IDC, there was a significant correlation between Ki67 and SUVmax (p=0.0030). The preoperative 18F-FDG PET/CT results of IDC patients had significant relationships with pathological status parameters. The determination of the preoperative SUVmax might help classify Luminal A and Luminal B patients among luminal-type breast cancer patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 5 2015 Neoadjuvant Chemotherapy with or without Concurrent Hormone Therapy in Estrogen Receptor-Positive Breast Cancer:NACED-Randomized Multicenter Phase II Trial 291 299 EN Kumi Sugiu Takayuki Iwamoto Catherine M. Kelly Naoki Watanabe Takayuki Motoki Mitsuya Itoh Shoichiro Ohtani Kenji Higaki Takako Imada Takeshi Yuasa Masako Omori Hiroshi Sonobe Toshiyoshi Fujiwara Junji Matsuoka Original Article 10.18926/AMO/53675 Although in the neoadjuvant setting for estrogen receptor (ER)-positive breast cancers, chemotherapy or hormone therapy alone does not result in satisfactory tumor response, it is unknown whether concurrent chemo-endocrine therapy is superior to chemotherapy alone in clinical outcomes. We conducted a randomized phase II trial to test the responses of ER-positive patients to concurrent administration of chemo-endocrine therapy in the neoadjuvant setting. Women with stage II-III, ER-positive, invasive breast cancer (n=28) received paclitaxel followed by fluorouracil, epirubicin, cyclophosphamide (T-FEC) and were randomized to receive concurrent chemo-endocrine therapy consisting of goserelin administered subcutaneously for premenopausal women or an aromatase inhibitor for postmenopausal women. The primary endpoint was the pathological complete response (pCR) rate after neoadjuvant therapy. Twenty-eight patients were randomized. There were no significant differences in pCR rate between the concurrent group (12.5%;2/16) and the chemotherapy alone group (8.3%;1/12). Tumor size after therapy was significantly reduced in the concurrent therapy group (p=0.035), but not in the chemotherapy-alone group (p=0.622). Neoadjuvant chemotherapy with concurrent hormone therapy provided no significant improvement in pCR rate in ER-positive breast cancers. These preliminary results should be followed up by further studies. No potential conflict of interest relevant to this article was reported.