Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Safety and Efficacy of a Well-Fitting Brassiere after Breast Reconstruction: A Qualitative Study 11 19 EN Satoko Watanabe Department of Plastic and Reconstructive Surgery, Okayama University Hospital Miho Saiga Department of Plastic and Reconstructive Surgery, Okayama University Hospital Takayuki Motoki Department of General Surgery, Okayama Saiseikai General Hospital Tadahiko Shien 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 Yoshihiro Kimata Department of Plastic and Reconstructive Surgery, Okayama University Hospital Original Article 10.18926/AMO/64356 The importance of a well-fitted, comfortable brassiere to overall quality of life after breast reconstruction has not been evaluated. Our aim was to determine the impact of a semi-customized brassiere on patients’ health-related quality of life after breast reconstruction. The subjects were prospective patients with mastectomy who were to undergo immediate or delayed breast reconstruction at our hospital. After surgery, a professional bra fitter sized each patient for a semi-customized brassiere and provided follow-up consultations. A self-reported questionnaire on breast aesthetics, postoperative pain, and satisfaction was used to assess the primary outcomes. Data were prospectively collected at baseline (before surgery) and at 1, 3, 6, and 12 months after surgery and analyzed. Forty-six patients (50 breasts) were included in the analysis. Consistent wearing of the brassiere reduced pain (p<0.05), with good overall satisfaction (p<0.001). Aesthetic scores on breast shape and size were higher with than without the custom brassiere at 3 months (p=0.02) and 6 months (p=0.03) after surgery. Wearing the brassiere reduced anxiety at all time points of measurement. A well-fitting brassiere ensured safety and provided a high degree of satisfaction without anxiety for patients after breast reconstruction. 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.

Elsevier Acta Medica Okayama 09609776 56 2021 Prospective cohort study of febrile neutropenia in breast cancer patients administered with neoadjuvant and adjuvant chemotherapies: CSPOR-BC FN study 70 77 EN Takashi Ishikawa Department of Breast Surgery and Oncology, Tokyo Medical University Kentaro Sakamaki Department of Biostatistics, Yokohama City University Kazutaka Narui Department of Biostatistics, Yokohama City University Hideki Nishimura Department of Biostatistics, Yokohama City University Takafumi Sangai Department of Breast and Thyroid Surgery, Chiba University Kentaro Tamaki Naha-Nishi Clinic Yoshie Hasegawa Department of Breast Surgery, Hirosaki Municipal Hospita Ken-ichi Watanabe Department of Breast Surgery, Hokkaido Cancer Center Nobuyasu Suganuma Department of Breast and Thyroid Surgery, Kanagawa Cancer Center Shintaro Michishita Department of Breast Surgery, Yao Municipal Hospital Sadatoshi Sugae Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine Tomohiko Aihara Breast Center, Aihara Hospital Koichiro Tsugawa Department of Breast and Thyroid Surgery, St. Marianna University Hirose Kaise Department of Breast Surgery and Oncology, Tokyo Medical University Naruto Taira Department of Breast and Endocrinology Surgery, Okayama University Graduate School of Medicine Hirofumi Mukai Division of Oncology/Hematology, National Cancer Center Hospital East Background<br/> As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). <br/> Patients and methods<br/> Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians’ discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. <br/> Results<br/> Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. <br/> Conclusions<br/> FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0960-9776 55 2020 Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer 63 68 EN Junji Tsurutani Advanced Cancer Translational Research Institute, Showa University Fumikata Hara Department of Breast Medical Oncology, Cancer Institute Hospital of JFCR Masahiro Kitada Department of Breast Disease Center, Asahikawa Medical University Hospital Masato Takahashi NHO Hokkaido Cancer Center Yuichiro Kikawa Department of Breast Surgery, Kobe City Medical Center General Hospita Hiroaki Kato Teine Keijinkai Hospital Eiko Sakata Niigata City General Hospital Yoichi Naito Department of Breast and Medical Oncology, National Cancer Center Hospital East Yoshie Hasegawa Department of Breast Surgery, Hirosaki Municipal Hospital Tsuyoshi Saito Japanese Red Cross Saitama Hospital Tsutomu Iwasa Department of Medical Oncology, Kindai University Faculty of Medicine Naruto Taira Okayama University Hospital Tsutomu Takashima Osaka City University Graduate School of Medicine Kosuke Kashiwabara Clinical Research Promotion Center, The University of Tokyo Hospital Tomohiko Aihara Breast Center, Aihara Hospital Hirofumi Mukai National Cancer Center Hospital East, Kashiwa Background</br> Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.</br> Methods</br> We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.</br> Results</br> One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.</br> Conclusions</br> Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC. 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.

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.

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.

BioMed Central Ltd. Acta Medica Okayama 1471-2407 13 2013 Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese women EN Taeko Mizoo Naruto Taira Keiko Nishiyama Tomohiro Nogami Takayuki Iwamoto Takayuki Motoki Tadahiko Shien Junji Matsuoka Hiroyoshi Doihara Setsuko Ishihara Hiroshi Kawai Kensuke Kawasaki Youichi Ishibe Yutaka Ogasawara Yoshifumi Komoike Shinichiro Miyoshi Background: Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. Methods: A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. Results: High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR = 1.37 [95% CI: 1.11-1.70]), rs3757318 (OR = 1.33[1.05-1.69]), and rs3803662 (OR = 1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. Conclusion: In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0167-6806 143 2 2014 Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers 403 409 EN Mitsuya Itoh Takayuki Iwamoto Junji Matsuoka Tomohiro Nogami Takayuki Motoki Tadahiko Shien Naruto Taira Naoki Niikura Naoki Hayashi Shoichiro Ohtani Kenji Higaki Toshiyoshi Fujiwara Hiroyoshi Doihara W. Fraser Symmans Lajos Pusztai We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (<Emphasis Type="ItalicUnderline">n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0171-5216 138 5 2012 DNA methylation status of REIC/Dkk-3 gene in human malignancies 799 809 EN Tatsuro Hayashi Hiroaki Asano Shinichi Toyooka Kazunori Tsukuda Junichi Soh Tadahiko Shien Naruto Taira Yuho Maki Norimitsu Tanaka Hiroyoshi Doihara Yasutomo Nasu Nam-ho Huh Shinichiro Miyoshi The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group. REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 1 2014 早期乳癌におけるOne-step Nucleic Acid Amplification(OSNA)法によるセンチネルリンパ節転移診断の検討 25 30 EN Taeko Mizoo Tadahiko Shien Maiko Ito Tomohiro Nogami Takayuki Iwamoto Takayuki Motoki Naruto Taira Junji Matsuoka Hiroyoshi Doihara 　Introduction: The one-step nucleic acid amplification (OSNA) assay is a new method to detect sentinel lymph node (SLN) metastases using cytokeratin 19 (CK19) mRNA in early breast cancer. Here we retrospectively analyzed the advantages and disadvantages of the OSNA assay. 　Methods: In a trial period, SLNs were divided into two sections, and we examined one side using the OSNA assay. The other side was examined by pathologists. After this period, we examined whole SLNs using only the OSNA assay. The patients with positive nodes by OSNA assay and/or pathology required axillary dissection. 　Results: We examined 27 primary breast cancer patients (36 SLNs) during the trial period. The overall concordance rate between the OSNA assay and pathology results was 91%. In the later period, 157 patients (217 SLNs) were examined. The CK19-positive rate obtained by the OSNA assay was 16.5% (macrometastases OSNA (++) : 7.2%, micrometastases OSNA (+) : 9.2%). The non-SLN positive rate among the CK19-positivecases was 23%. The OSNA assay's false negative was one case in which the expression of CK-19 on the primary tumor and lymph node was not detected. 　Conclusions: Our OSNA assay results were comparable to those obtained using a conventional pathological technique. Pathologists and laboratory technicians could save time and effort by using the OSNA assay when seeking the precise diagnosis during surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 67 3 2013 p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer. 165 170 EN Tadahiko Shien Takayuki Kinoshita Kunihiko Seki Miwa Yoshida Takashi Hojo Chikako Shimizu Naruto Taira Hiroyoshi Doihara Sadako Akashi-Tanaka Hitoshi Tsuda Yasuhiro Fujiwara Original Article 10.18926/AMO/50409 While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p＝0.045) and histological grade 3 (p＝0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 67 3 2013 Association between Mammographic Breast Density and Lifestyle in Japanese Women 145 151 EN Setsuko Ishihara Naruto Taira Kensuke Kawasaki Youichi Ishibe Taeko Mizoo Keiko Nishiyama Takayuki Iwamoto Tomohiro Nogami Takayuki Motoki Tadahiko Shien Junji Matsuoka Hiroyoshi Doihara Yoshifumi Komoike Shuhei Sato Susumu Kanazawa Original Article 10.18926/AMO/50407 A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, －0.403;p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, －0.196;p value, 0.0143) and number of deliveries (parameter estimate, －0.388;p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s. No potential conflict of interest relevant to this article was reported.

Springer Japan Acta Medica Okayama 1880-4233 2012 Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1–3 lymph node metastases EN Tomohiro Nogami Tadahiko Shien Takehiro Tanaka Keiko Nishiyama Taeko Mizoo Takayuki Iwamto Hirokuni Ikeda Naruto Taira Hiroyoshi Doihara Shinichiro Miyoshi Background Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer. Methods From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS). Results Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037). Conclusion Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1–3 metastatic lymph nodes. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 66 4 2012 Ectopic Cervical Thymoma:A Case Report with 18F-fluorodeoxyglucose Positron Emission Tomography Findings 357 361 EN Kazuhiko Shien Tadahiko Shien Junichi Soh Hirokuni Ikeda Tomohiro Nogami Naruto Taira Hiroyoshi Doihara Shinichiro Miyoshi Case Report 10.18926/AMO/48691 Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of ¹⁸F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 4 2011 Clinical Efficacy of Capecitabine and Cyclophosphamide (XC) in Patients with Metastatic Breast Cancer 231 237 EN Tadahiko Shien Hiroyoshi Doihara Keiko Nishiyama Hiroko Masuda Tomohiro Nogami Hirokuni Ikeda Naruto Taira Original Article 10.18926/AMO/46848 Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH), to evaluate responses to XC, adverse events and time to progression (TTP). Twenty patients with MBC received XC between 2006 and 2009. With the exception of 2 elderly patients who were over the age of 70 at the initial examination, all of the patients had received prior treatment with an anthracycline and/or a taxane. No complete response (CR) cases were observed, but partial response (PR) was achieved in 6 patients (30%) and SD in 9 (45%), of whom 5 (20%) sustained SD status for >12 months. The median TTP was 6 months (range:3-27 mo.). Three patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis), but no other patients developed adverse reactions causing interruption of the therapy. XC was safe even in previously treated and elderly MBC patients;moreover, it yielded remarkable clinical responses. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0167-6806 128 3 2011 Associations among baseline variables, treatment-related factors and health-related quality of life 2 years after breast cancer surgery 735 747 EN Naruto Taira Kojiro Shimozuma Takeru Shiroiwa Shozo Ohsumi Katsumasa Kuroi Shigehira Saji Mitsue Saito Shigemichi Iha Takanori Watanabe Noriyuki Katsumata Provision of social support and rehabilitation for patients with physical, mental, and functional problems after cancer treatment is important for long-term health-related quality of life (HRQOL). Effective use of human and financial healthcare resources requires identification of patients requiring rehabilitation. The objectives of the current study were to clarify the patterns of physical and psychosocial recovery over time, to evaluate the associations among baseline variables, treatment-related factors and HRQOL at 6 months, 1, and 2 years after breast cancer surgery, and to identify the significant factors predicting HRQOL at each point. A multicenter longitudinal study was performed to evaluate physical conditions, anxiety, depression, and HRQOL at 1 month (baseline), 6 months, 1, and 2 years after surgery in 196 patients (mean age: 53.3 years old) with early breast cancer and no postoperative recurrence. Physical conditions were evaluated using a patient-reported symptom checklist. HRQOL was rated using the functional assessment of cancer treatment scalegeneral (FACT-G) and the breast cancer subscale (FACTB). Anxiety and depression were rated using the hospital anxiety and depression scale (HADS). More than 50% of patients had local problems of "tightness", "arm weakness." and "arm lymphedema", and systemic problems of "reduced energy, fatigue, and general weakness" postoperatively. The HRQOL score significantly improved 1 year after surgery, and scores for physical, emotional and functional well-being also increased with time, whereas the score for social well-being was the highest at baseline and decreased with time. Depression and anxiety significantly improved with time. Concomitant disease, marital status, and the presence of a partner, anxiety and depression at baseline, pathological lymph node involvement, and adjuvant intravenous chemotherapy were significant factors predicting FACT-G scores at 6 months, 1, and 2 years after surgery. Depression at baseline was a strong predictor of HRQOL up to 2 years after surgery. These results suggest that physical rehabilitation is required for tightness and lymphedema to improve long-term postoperative physical function. A further study of psychosocial interventions is required to improve depression and social well-being after breast cancer surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 63 4 2009 Efficacy and Tolerability of Weekly Paclitaxel in Combination with High-dose Toremifene Citrate in Patients with Metastatic Breast Cancer 187 194 EN Atsushi Okita Toshiaki Saeki Kenjiro Aogi Shozo Osumi Shigemitsu Takashima Riki Okita Naruto Taira Tomokazu Kakishita Akira Kurita Original Article 10.18926/AMO/31816 <p>Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 60 1 2006 Gefitinib, an epidermal growth factor receptor blockade agent, shows additional or synergistic effects on the radiosensitivity of esophageal cancer cells in vitro. 25 34 EN Naruto Taira Hiroyoshi Doihara Tetsuya Oota Fumikata Hara Tadahiko Shien Hirotoshi Takahashi Seiji Yoshitomi Youichi Ishibe Nobuyoshi Shimizu Article 10.18926/AMO/30755 <p>Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy.</p> No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 3 2008 I 乳がんの診断と治療 273 283 EN Hiroyoshi Doihara Naruto Taira No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2006 Gefitinib, an Epidermal Growth Factor Receptor Blockade Agent, Shows Additional or Synergistic Effects on the Radiosensitivity of Esophageal Cancer Cells in Vitro EN Naruto Taira No potential conflict of interest relevant to this article was reported.