Faculty Profiles - SHIEN Tadahiko

Papers - SHIEN Tadahiko

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[III. Fertility preservation for breast cancer patients--approach at our institution]. Reviewed

Hiroyoshi Doihara, Tadahiko Shien

Gan to kagaku ryoho. Cancer & chemotherapy 42 ( 13 ) 2444 - 6 2015.12

Unmet Information Needs and Quality of Life in Young Breast Cancer Survivors in Japan Reviewed

Mika Miyashita, Shinji Ohno, Akemi Kataoka, Eriko Tokunaga, Norikazu Masuda, Tadahiko Shien, Kimiko Kawabata, Miyako Takahashi

CANCER NURSING 38 ( 6 ) E1 - E11 2015.11

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background: Young breast cancer survivors have specific needs related to age. Clarifying the relationships between unmet information needs and quality of life (QOL) in young breast cancer survivors can contribute to constructing a support system to enhance QOL in patients.
Objective: This study aimed to identify the unmet information needs and examine the relationships between unmet information needs and QOL in young breast cancer survivors in Japan.
Methods: Participants completed an information needs questionnaire containing 26 items, the World Health Organization Quality of Life Instrument-Short Form (WHOQOL-BREF), and a demographic and medical information questionnaire.
Results: Fifty participants (30.7%) were unsatisfied with overall communication with medical professionals. The mean scores on all subscales of the WHOQOL-BREF of the participants who were satisfied with overall communication with medical professionals were significantly higher than those of the unsatisfied group. follow-up tests, treatment for recurrence of breast cancer, strategies about communication with medical staff, and nutrition were significantly related with all subscales in the WHOQOL-BREF. Secondary menopause caused by hormonal therapy was significantly related with physical and psychological health.
Conclusions: Japanese young breast cancer survivors have unmet information needs, including age-specific issues. These unmet information needs are related to QOL. In particular, overall communication with medical professionals, which is the most unmet information need, is related to QOL.
Implications for Practice: Oncology nurses should teach patients communication skills, provide adequate information, and provide education and emotional support to medical professionals to improve QOL in young breast cancer survivors.

DOI： 10.1097/NCC.0000000000000201

Impact of modifiable lifestyle factors on outcomes after breast cancer diagnosis: the Setouchi Breast Cancer Cohort Study. Reviewed International journal

Naruto Taira, Ichiro Akiyama, Setsuko Ishihara, Youichi Ishibe, Kensuke Kawasaki, Makoto Saito, Tadahiko Shien, Tsunehisa Nomura, Fumikata Hara, Taeko Mizoo, Yuri Mizota, Seiichiro Yamamoto, Shozo Ohsumi, Hiroyoshi Doihara

Japanese journal of clinical oncology 45 ( 6 ) 600 - 2 2015.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

The primary purpose of this large cohort study is to investigate the effects on breast cancer outcomes of modifiable lifestyle factors after breast cancer diagnosis. These factors include physical activity, smoking, alcohol consumption, obesity and weight gain after diagnosis, alternative medicine and dietary factors. Women diagnosed with Stage 0 to III breast cancer are eligible for participation to this study. Lifestyle, use of alternative medicine, psychosocial factors, reproductive factors and health-related quality of life will be assessed using a questionnaire at the time of breast cancer diagnosis (baseline), and 1, 2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes will be obtained from a breast cancer database. The primary endpoint will be disease-free survival. Secondary endpoints are overall survival, health-related quality of life, breast cancer-related symptoms and adverse events. Patient recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients is planned during the 5-year recruitment period. The concept of the study is described in this article.

DOI： 10.1093/jjco/hyv033

Assessment of the prognostic and predictive ability of a gene signature compared to histological grade in estrogen receptor positive, HER2 negative breast cancer Reviewed

Iwamoto Takayuki, Kelly Catherine, Bianchini Giampalo, Mizoo Takeo, Nogami Tomohiro, Motoki Takayuki, Shien Tadahiko, Taira Naruto, Hayashi Naoki, Niikura Naoki, Fujiwara Toshiyoshi, Doihara Hiroyoshi, Matsuoka Junji

CANCER RESEARCH 75 2015.5

Change in estrogen receptor, HER2, and Ki-67 status between primary breast cancer and ipsilateral breast cancer tumor recurrence. Reviewed International journal

Y Okumura, R Nishimura, K Nakatsukasa, A Yoshida, N Masuda, M Tanabe, T Shien, S Tanaka, N Arima, Y Komoike, T Taguchi, T Iwase, H Inaji, M Ishitobi

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 41 ( 4 ) 548 - 52 2015.4

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Changes in the biological marker status between primary and recurrent tumors are observed in breast cancer. However, their clinical significance is still uncertain, especially for patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery. PATIENTS AND METHODS: A total of 117 patients with IBTR without distant metastases were enrolled in this study. All patients were examined for estrogen receptor (ER), HER2, and Ki-67 in both the primary tumors and paired IBTR. We evaluated the impact of changes in these biomarkers between primary tumors and IBTR on the prognosis after IBTR. RESULTS: There were no associations of changes in the ER, HER2 status with distant disease-free survival (DDFS) after surgical resection of IBTR, whereas the change in the Ki-67 status between the primary tumors and IBTR was significantly correlated with DDFS (unadjusted: p = 0.0094; adjusted: p = 0.013). Patients in the "increased or remained high" Ki-67 group had a significantly shorter DDFS than those in the "decreased or remained low" Ki-67 group (5-year DDFS: 55.5 vs. 79.3%, respectively, p = 0.0084 by log-rank test). CONCLUSION: An increased or persistently high Ki-67 status in the IBTR was significantly correlated with a poorer prognosis after IBTR.

DOI： 10.1016/j.ejso.2015.01.030

Other Link： http://orcid.org/0000-0001-5536-132X

Correlation between 18F-fluorodeoxyglucose Positron Emission Tomography/computed Tomography and Clinicopathological Features in Invasive Ductal Carcinoma of the Breast. Reviewed

Maiko Ito, Tadahiko Shien, Mitsumasa Kaji, Taeko Mizoo, Takayuki Iwamoto, Tomohiro Nogami, Takayuki Motoki, Naruto Taira, Hiroyoshi Doihara, Shinichiro Miyoshi

Acta medica Okayama 69 ( 6 ) 333 - 8 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/53907

Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401) Reviewed

Tadahiko Shien, Hiroji Iwata, Kenjiro Aogi, Takashi Fukutomi, Kenichi Inoue, Takayuki Kinoshita, Masato Takahashi, Akira Matsui, Taro Shibata, Haruhiko Fukuda

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 19 ( 6 ) 982 - 988 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Cancer subtype has recently become an increasingly important consideration when deciding the treatment strategy for breast cancer. For the estrogen receptor positive (ER+) subtype, the efficacy of adjuvant endocrine therapy is definitive, but that of adjuvant chemotherapy is controversial.
In order to evaluate the effect of adding doxorubicin (A) and cyclophosphamide (C) to tamoxifen (TAM) (ACT) on the overall survival (OS) of node-positive postmenopausal breast cancer (PMBC) patients, we conducted a randomized trial. Eligibility criteria included pathologically node-positive (n = 1-9) PMBC, stage I-IIIA disease. Patients were randomized to receive either TAM (20 mg daily) for 2 years or A (40 mg/m(2)) and C (500 mg/m(2)) plus TAM (ACT) as adjuvant therapy following surgery.
One hundred twenty-nine patients were recruited (TAM 64, ACT 65) between October 1994 and July 1999. The hazard ratios for OS and relapse-free survival (RFS) were 0.58 (95 % CI 0.24-1.39; log-rank p = 0.22) and 0.45 (95 %CI 0.24-0.86; log-rank p = 0.013), respectively, in favor of ACT. The 5-year OS and RFS were 76.9 % (ER+ 87.1 %, ER- 53.3 %) and 54.9 % (ER+ 59.3 %, ER- 42.9 %) for TAM and 85.0 % (ER+ 90.0 %, ER- 77.1 %) and 76.7 % (ER+ 76.9 %, ER- 76.0 %) for ACT. A higher proportion of the patients receiving ACT than those receiving TAM experienced grade 3 decreased white blood cell count and grade 2-3 nausea.
The efficacy of adding AC to TAM was not high for ER+, node-positive PMBC. However, adjuvant ACT therapy was considered to be effective for ER-, node-positive PMBC.

DOI： 10.1007/s10147-013-0657-z

Repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: the impact of radiotherapy on second IBTR Reviewed

Makoto Ishitobi, Yasuhiro Okumura, Reiki Nishimura, Katsuhiko Nakatsukasa, Masahiko Tanabe, Atsushi Yoshida, Norikazu Masuda, Tadahiko Shien, Satoru Tanaka, Yoshifumi Komoike, Nobuyuki Arima, Tetsuya Taguchi, Hideo Inaji

BREAST CANCER 21 ( 6 ) 754 - 760 2014.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). Especially, the impact of radiotherapy (RT) on a second IBTR is unknown.
We retrospectively analyzed 143 patients from 8 institutions in Japan who underwent repeat lumpectomy after IBTR. The risk factors of a second IBTR were assessed.
The median follow-up period was 4.8 years. The 5-year second IBTR-free survival rate was 80.7 %. There was a significant difference in the second IBTR-free survival rate according to RT (p = 0.0003, log-rank test). The 5-year second IBTR-free survival rates for patients who received RT after initial surgery, RT after salvage surgery, and no RT were 78.0, 93.5, and 52.7 %, respectively. Multivariate analysis revealed that RT was a significantly independent predictive factor of second IBTR-free survival.
Repeat lumpectomy plus RT is a reasonable option in patients who did not undergo RT at the initial surgery. In contrast, caution is needed when RT is omitted in patients who have undergone repeat lumpectomy.

DOI： 10.1007/s12282-013-0454-6

The discordance between primary breast cancer lesions and pulmonary metastatic lesions in expression of aldehyde dehydrogenase 1-positive cancer cells Reviewed

Tomohiro Nogami, Tadahiko Shien, Takehiro Tanaka, Hiroyoshi Doihara, Naruto Taira, Daisuke Takabatake, Rieko Nishimura, Keiko Nishiyama, Taeko Mizoo, Shozo Ohsumi

BREAST CANCER 21 ( 6 ) 698 - 702 2014.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients.
We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors.
None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively.
There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.

DOI： 10.1007/s12282-013-0445-7

Clinicopathological features of young patients (< 35 years of age) with breast cancer in a Japanese Breast Cancer Society supported study Reviewed

Akemi Kataoka, Eriko Tokunaga, Norikazu Masuda, Tadahiko Shien, Kimiko Kawabata, Mika Miyashita

BREAST CANCER 21 ( 6 ) 643 - 650 2014.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

To clarify the clinicopathological features of breast cancer in young females, surveillance data of the Registration Committee of the Japanese Breast Cancer Society were analyzed.
The clinicopathological characteristics were compared between young (< 35) patients and non-young (a parts per thousand yen35) patients among 109,617 records registered between 2004 and 2009.
The numbers of young and non-young patients were 2,982 (2.7 %) and 106,295 (97.0 %), respectively. The young patients had more cases of a familial history of breast cancer, more subjective symptoms, fewer bilateral tumors, lower BMIs, larger tumors, more positive lymph nodes, fewer instances of an ER-positive status, more instances of an HER2-positive status, more triple-negative tumors and more advanced TNM stages. The young patients more frequently received neoadjuvant chemotherapy and breast-conserving therapy (BCT) compared with the non-young patients. Eighty percent of all patients received adjuvant therapy. The young patients were more frequently treated with chemotherapy, molecular targeted therapy and radiation therapy than the non-young patients.
In this study, young patients with breast cancer were diagnosed at more advanced stages and had more endocrine-unresponsive tumors than non-young patients. Further prognostic analyses should be conducted in this cohort.

DOI： 10.1007/s12282-013-0466-2

Fertility preservation in breast cancer patients Reviewed

Tadahiko Shien, Mikiya Nakatsuka, Hiroyoshi Doihara

BREAST CANCER 21 ( 6 ) 651 - 655 2014.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Systemic therapies have been shown to effectively improve prognosis in patients with breast cancer. However, such therapies also become increasingly harmful as their duration increases, and they have adverse effects on fertility and ovarian function. Fertility preservation (FP) is important in young adult cancer survivors who may wish to have children. In Japan, some cancer societies recommend that the potentially serious effects of systemic therapy on ovarian function should be explained to women with cancer, and they should be encouraged to undergo FP prior to commencing treatment. Still, as there are no official guidelines, many oncologists lack the required knowledge and mind-set to advise young breast cancer patients on fertility issues. Counseling of patients and their families might improve their understanding about the influence of such treatment on fertility and ensure effective FP. There are several FP methods that can be selected before beginning treatment, and these methods have both advantages and disadvantages. Young adults with breast cancer who want to bear children in the future must be provided with FP counseling, in addition to advice about breast cancer treatment and prognosis.

DOI： 10.1007/s12282-013-0463-5

Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology Group Study 9404. Reviewed International journal

Tadahiko Shien, Hiroji Iwata, Takashi Fukutomi, Kenichi Inoue, Kenjiro Aogi, Takayuki Kinoshita, Jiro Ando, Seiki Takashima, Kenichi Nakamura, Taro Shibata, Haruhiko Fukuda

Cancer chemotherapy and pharmacology 74 ( 3 ) 603 - 9 2014.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

PURPOSE: A prospective randomized clinical trial was conducted to evaluate the efficacy of tamoxifen plus doxorubicin and cyclophosphamide compared to tamoxifen plus tegafur-uracil as an adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC). METHODS: Eligibility criteria included pathologically node-positive (n = 1-9) preMBC with curative resection, in stages I-IIIA. Patients were randomized to receive either tamoxifen 20 mg/day plus tegafur-uracil 400 mg/day (TU) for 2 years or six courses of a 28-day cycle of doxorubicin 40 mg/m(2) plus cyclophosphamide 500 mg/m(2) on day 1 along with tamoxifen (ACT) given for 2 years as adjuvant therapy. Primary endpoint was overall survival (OS), and secondary endpoint was recurrence-free survival (RFS). RESULTS: In total, 169 patients were recruited (TU arm 87, ACT arm 82) between October 1994 and September 1999. The HR for OS was 0.76 (95 % CI 0.35, 1.66, log-rank p = 0.49) and that for RFS was 0.77 (95 % CI 0.44, 1.36, log-rank p = 0.37), with ACT resulting in a better HR. The 5-year OS was 79.7 % for patients in the TU arm and 83 % for those in the ACT arm. The 5-year RFS was 66.1 % for patients in the TU arm and 70.6 % for those in the ACT arm. A higher proportion of patients in the ACT arm experienced grade 3 leucopenia (0 % in the TU arm, 4 % in the ACT arm). CONCLUSIONS: There were no significant differences in the efficacy of TU and ACT as adjuvant therapy.

DOI： 10.1007/s00280-014-2545-2

Fertility concerns and preservation strategies in young women with breast cancer Reviewed

Tadahiko Shien

JOURNAL OF THORACIC DISEASE 6 ( 6 ) 581 - 583 2014.6

Resection of the primary tumor in stage IV breast cancer Reviewed

Tadahiko Shien, Hiroyoshi Doihara

World Journal of Clinical Oncology 5 ( 2 ) 82 - 85 2014.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Baishideng Publishing Group Co., Limited

Stage IV breast cancer refers to breast cancer that has already metastasized to distant regions when initially diagnosed. Treatment for stage IV is intended to "prolong survival and palliate symptoms". Resection of a primary tumor is considered to be "effective only at alleviating chest symptoms and providing local control" in spite of the advances of imaging examination and medication for breast cancer. Molecular target and endocrine drugs are very effective and useful to tailor-make a treatment strategy according to breast cancer subtypes. Positron emission tomography-computed tomography can detect and diagnose the very small metastases and recurrences which can potentially be cured even if they are distant metastases. Recently, many retrospective studies have reported the survival benefit of surgery for breast cancer patients with metastases and some clinical trials which confirm the surgical prognostic benefit for them have started to enrol patients. The goal of treatment has to be clearly identified: increase the patient's survival time, provide local control or perform histology to determine the cancer's properties. The best evidence is absolutely essential to treat patients who need surgery at the right time. We need to evaluate the treatment strategy, including primary resection for stage IV breast cancer particularly, and find new evidence by prospective analysis.

DOI： 10.5306/wjco.v5.i2.82

A case of carcinoma showing thymus-like differentiation with a rapidly lethal course Reviewed

Tomohiro Nogami, Naruto Taira, Shinichi Toyooka, Takehiro Tanaka, Taeko Mizoo, Takayuki Iwamoto, Tadahiko Shien, Junichi Soh, Shinichiro Miyoshi, Hiroyoshi Doihara

Case Reports in Oncology 7 ( 3 ) 840 - 844 2014.4

Language：English Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

A 55-year-old woman underwent a total thyroidectomy for carcinoma showing thymus-like differentiation (CASTLE). The patient was referred to our hospital after the tumor was found to have directly invaded the cervical esophagus and the entire circumference of the trachea. A total thyroidectomy was performed, followed by end-to-end anastomosis of the trachea, suprahyoid release and dissection of bilateral pulmonary ligaments. No major complications, including anastomotic dehiscence or stenosis, were observed. The patient experienced some swallowing disturbances and hoarseness during the perioperative period but fully recovered. Radiotherapy to the neck was performed as an adjuvant therapy. Eleven months after surgery, lower back pain and right leg numbness developed and led to gait inability. Multiple lung and bone recurrences were observed, but no local recurrence. Palliative radiotherapy to the bone metastasis was performed. The patient died of pleural metastasis 14 months after the initial diagnosis of CASTLE.

DOI： 10.1159/000370306

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 Reviewed

Tomohiro Nogami, Tadahiko Shien, Takehiro Tanaka, Keiko Nishiyama, Taeko Mizoo, Takayuki Iwamto, Hirokuni Ikeda, Naruto Taira, Hiroyoshi Doihara, Shinichiro Miyoshi

BREAST CANCER 21 ( 1 ) 58 - 65 2014.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

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.
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).
Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037).
Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1-3 metastatic lymph nodes.

DOI： 10.1007/s12282-012-0350-5

Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers Reviewed

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

BREAST CANCER RESEARCH AND TREATMENT 143 ( 2 ) 403 - 409 2014.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

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.

DOI： 10.1007/s10549-013-2763-z

Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese women Reviewed

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

BMC CANCER 13 565 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

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.

DOI： 10.1186/1471-2407-13-565

Breast cancer subtype and distant recurrence after ipsilateral breast tumor recurrence. Reviewed International journal

Makoto Ishitobi, Yasuhiro Okumura, Nobuyuki Arima, Atsushi Yoshida, Katsuhiko Nakatsukasa, Takuji Iwase, Tadahiko Shien, Norikazu Masuda, Satoru Tanaka, Masahiko Tanabe, Takehiro Tanaka, Yoshifumi Komoike, Tetsuya Taguchi, Reiki Nishimura, Hideo Inaji

Annals of surgical oncology 20 ( 6 ) 1886 - 92 2013.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

BACKGROUND: There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR). METHODS: One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR. RESULTS: There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model). CONCLUSIONS: Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).

DOI： 10.1245/s10434-012-2825-1

p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer Reviewed

Tadahiko Shien, Takayuki Kinoshita, Kunihiko Seki, Miwa Yoshida, Takashi Hojo, Chikako Shimizu, Naruto Taira, Hiroyoshi Doihara, Sadako Akashi-Tanaka, Hitoshi Tsuda, Yasuhiro Fujiwara

ACTA MEDICA OKAYAMA 67 ( 3 ) 165 - 170 2013.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 = 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.

DOI： 10.18926/AMO/50409

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