Faculty Profiles - SHIEN Tadahiko

Papers - SHIEN Tadahiko

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Association between mammographic breast density and lifestyle in japanese women Reviewed

Setsuko Ishihara, Naruto Taira, Kensuke Kawasakic, Youichi Ishibe, Taeko Mizoo, Keiko Nishiyama, Takayuki Iwamoto, Tomohiro Nogami, Takayuki Motoki, Tadahiko Shieir, Junji Matsuoka, Hiroyoshi Doihara, Yoshifumi Komoike, Shuhei Sato, Susumu Kanazawa

Acta Medica Okayama 67 ( 3 ) 145 - 151 2013

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

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 per- formed. 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 cor- related 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. © 2013 by Okayama University Medical School.

DOI： 10.18926/AMO/50407

A Randomized Controlled Trial Comparing Primary Tumour Resection Plus Systemic Therapy With Systemic Therapy Alone in Metastatic Breast Cancer (PRIM-BC): Japan Clinical Oncology Group Study JCOG1017 Reviewed

Tadahiko Shien, Kenichi Nakamura, Taro Shibata, Takayuki Kinoshita, Kenjiro Aogi, Tomomi Fujisawa, Norikazu Masuda, Kenichi Inoue, Haruhiko Fukuda, Hiroji Iwata

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 42 ( 10 ) 970 - 973 2012.10

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

This trial is being conducted to confirm the superiority, in terms of overall survival, of primary tumour resection plus systemic therapy to systemic therapy alone in patients with Stage IV breast cancer who are not refractory to primary systemic therapy. The inclusion criteria for the study are as follows: untreated patients with histologically confirmed invasive breast cancer with one or more measurable metastatic lesions diagnosed by radiological examination. All patients receive primary systemic therapy according to the estrogen receptor and human epidermal growth factor receptor type-2 status of the primary breast cancer after the first registration. After 3 months, the patients without disease progression are randomized to the primary tumour resection plus systemic therapy arm or the systemic therapy alone arm. The primary endpoint is the overall survival, and the secondary endpoints are proportion of patients without tumour progression at the metastatic sites, yearly local recurrence-free survival, proportion of local ulcer/local bleeding, yearly primary tumour resection-free survival, adverse events of chemotherapy, operative morbidity and serious adverse events. The patient recruitment was commenced in May 2011. Enrolment of 410 patients for randomization is planned over a 5 year recruitment period. We hereby report the details of the study.

DOI： 10.1093/jjco/hys120

Ectopic Cervical Thymoma: A Case Report with F-18-fluorodeoxyglucose Positron Emission Tomography Findings Reviewed

Kazuhiko Shien, Tadahiko Shien, Junichi Soh, Hirokuni Ikeda, Tomohiro Nogami, Naruto Taira, Hiroyoshi Doihara, Shinichiro Miyoshi

ACTA MEDICA OKAYAMA 66 ( 4 ) 357 - 361 2012.8

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

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 F-18-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.

DOI： 10.18926/AMO/48691

DNA methylation status of REIC/Dkk-3 gene in human malignancies Reviewed

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

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 138 ( 5 ) 799 - 809 2012.5

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

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.

DOI： 10.1007/s00432-012-1158-6

意思決定におけるピアサポート効果術後パートナーとの関係に不安を持つ一事例を通して

露無祐子, 小野美穂, 岡田知子, 渡部聡子, 元木崇之, 枝園忠彦, 平成人, 松岡順治, 木股敬裕, 土井原博義

日本乳癌学会総会プログラム抄録集 20回 550 - 550 2012.5

A radial sclerosing lesion mimicking breast cancer on mammography in a young woman Reviewed

Masashi Furukawa, Naruto Taira, Shigemichi Iha, Tomohiro Nogami, Tadahiko Shien, Masako Omori, Hiroyoshi Doihara

Case Reports in Oncology 5 ( 1 ) 99 - 103 2012.1

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

A spiculated mass on a mammogram is highly suggestive of malignancy. We report the case of a 32-year-old woman with a radial sclerosing lesion that mimicked breast cancer on mammography. She visited her physician after palpating a lump in her left breast. Mammography showed architectural distortion in the upper inner quadrant of the left breast. Ultrasonography showed a low echoic area with an ambiguous boundary. Core needle biopsy was performed because of the suspicion of malignancy. Histological examination did not reveal any malignant cells. After 6 months, the breast lump became larger and the patient was referred to our hospital. Mammography performed in our hospital showed a spiculated mass, and therefore mammotome biopsy was performed. Histological examination revealed dense fibroelastic stroma with a wide variety of mastopathic changes, leading to a diagnosis of a radial sclerosing lesion. One year after the biopsy, the lump on her left breast had disappeared and mammography showed no spiculated mass. Copyright © 2012 S. Karger AG, Basel.

DOI： 10.1159/000337024

Combination treatment with fulvestrant and various cytotoxic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) has a synergistic effect in estrogen receptor-positive breast cancer Reviewed

Hirokuni Ikeda, Naruto Taira, Tomohiro Nogami, Kazuhiko Shien, Masanori Okada, Tadahiko Shien, Hiroyoshi Doihara, Shinichiro Miyoshi

CANCER SCIENCE 102 ( 11 ) 2038 - 2042 2011.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Patients with estrogen receptor (ER)-positive breast cancers have a better prognosis than those with ER-negative breast cancers, but often have low sensitivity to chemotherapy and a limited survival benefit. We have previously shown a combination effect of taxanes and fulvestrant and suggested that this treatment may be useful for ER-positive breast cancer. In this study, we evaluated the effects of combinations of hormone drugs and chemotherapeutic agents. In vitro, the effects of combinations of five chemotherapeutic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) and three hormone drugs (fulvestrant, tamoxifen, and 4-hydroxytamoxifen) were examined in ER-positive breast cancer cell lines using CalcuSyn software. Changes in chemoresistant factors such as Bcl2, multidrug resistance-associated protein 1, and microtubule-associated protein tau were also examined after exposure of the cells to hormone drugs. In vivo, tumor sizes in mice were evaluated after treatment with docetaxel or doxorubicin alone, fulvestrant alone, and combinations of these agents. Combination treatment with fulvestrant and all five chemotherapeutic agents in vitro showed synergistic effects. In contrast, tamoxifen showed an antagonistic effect with all the chemotherapeutic agents. 4-Hydroxytamoxifen showed an antagonistic effect with doxorubicin and 5-fluorouracil, but a synergistic effect with taxanes and vinorelbine. Regarding chemoresistant factors, Bcl2 and microtubule-associated protein tau were downregulated by fulvestrant. In vivo, a combination of fulvestrant and docetaxel had a synergistic effect on tumor growth, but fulvestrant and doxorubicin did not show this effect. In conclusion, fulvestrant showed good compatibility with all the evaluated chemotherapeutic agents, and especially with docetaxel, in vitro and in vivo. (Cancer Sci 2011; 102: 2038-2042)

DOI： 10.1111/j.1349-7006.2011.02050.x

Clinical Efficacy of Capecitabine and Cyclophosphamide (XC) in Patients with Metastatic Breast Cancer Reviewed

Tadahiko Shien, Hiroyoshi Doihara, Keiko Nishiyama, Hiroko Masuda, Tomohiro Nogami, Hirokuni Ikeda, Naruto Taira

ACTA MEDICA OKAYAMA 65 ( 4 ) 231 - 237 2011.8

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

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.

DOI： 10.18926/AMO/46848

Functional interaction of fibroblast growth factor-8, bone morphogenetic protein and estrogen receptor in breast cancer cell proliferation Reviewed

Hiroko Masuda, Fumio Otsuka, Yoshinori Matsumoto, Mariko Takano, Tomoko Miyoshi, Kenichi Inagaki, Tadahiko Shien, Naruto Taira, Hirofumi Makino, Hiroyoshi Doihara

MOLECULAR AND CELLULAR ENDOCRINOLOGY 343 ( 1-2 ) 7 - 17 2011.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Estrogen is involved in the development and progression of breast cancer. Here we investigated the effect of fibroblast growth factor (FGF)-8 on breast cancer cell proliferation caused by estrogen using human breast cancer MCF-7 cells. MCF-7 cells express estrogen receptor (ER)alpha, ER beta, FGF receptors, and Smad signaling molecules. Estradiol stimulated MCF-7 cell proliferation in a concentration-responsive manner, whereas BSA-bound estradiol had a weak effect on MCF-7 cell mitosis compared with the effect of free estradiol. It is notable that estrogen-induced cell proliferation was enhanced in the presence of FGF-8 and that the combined effects were reversed in the presence of an FGF-receptor kinase inhibitor or an ER antagonist. It was also revealed that FGF-8 increased the expression levels of ER alpha, ER beta and aromatase mRNAs, while estradiol reduced the expression levels of ERs, aromatase and steroid sulfatase in MCF-7 cells. FGF-8-induced phosphorylation of FGF receptors was augmented by estradiol, which was reversed by an ER antagonist. FGF-8-induced activation of MAPKs and AKT signaling was also upregulated in the presence of estrogen. On the other hand, FGF-8 suppressed BMP-7 actions that are linked to mitotic inhibition by activating the cell cycle regulator cdc2. FGF-8 was revealed to inhibit BMP receptor actions including Id-1 promoter activity and Smad1/5/8 phosphorylation by suppressing expression of BMP type-II receptors and by increasing expression of inhibitory Smads. Collectively, the results indicate that FGF-8 acts to facilitate cell proliferation by upregulating endogenous estrogenic actions as well as by suppressing BMP receptor signaling in ER-expressing breast cancer cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.mce.2011.05.037

A case of the usage of entecavir to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patient Reviewed

Takayuki Muraoka, Naruto Taira, Tadahiko Shien, Hiroyoshi Doihara, Akinobu Takaki, Shinichiro Miyoshi

Japanese Journal of Cancer and Chemotherapy 38 ( 11 ) 1861 - 1864 2011

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.

Hepatitis B virus (HBV) reactivation is a serious clinical problem for HBV infected patients, and one of its possible causes is chemotherapy for malignant disease. At the onset of active hepatitis, planned chemotherapy should be discontinued and acute or fetal fulminant hepatitis must be induced in some cases. Therefore, it is desirable to prevent virus reactivation during chemotherapy in HBV-positive patients. We report a case in which adjuvant chemotherapy for a breast cancer patient was accomplished safely by using entecavir. The patient was a 48-year-old woman with breast cancer whose HBV infection had been pointed out when she was 20 years old. Breast reconstruction was performed, followed by mastectomy. Pathological findings were invasive ductal carcinoma, three positive nodes, estrogen and progesterone receptor-positive, and HER2-negative. An adjuvant chemotherapy with anthracycline followed by taxane was planned. Blood chemistry revealed the seroconversion of HBV and the quantity of HBV-DNA was 2. 8 log copies/mL. Administration of the anti-virus agent, entecavir, was started three weeks before chemotherapy. The HBV-DNA was decreased under the titer of detection and no re-increase in HBV-DNA was found during chemotherapy. Planned chemotherapy was accomplished safely without HBV reactivation.

The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells Reviewed

Hirokuni Ikeda, Naruto Taira, Fumikata Hara, Takeo Fujita, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka, Tomohiro Nogami, Tadahiko Shien, Hiroyoshi Doihara, Shinichiro Miyoshi

BREAST CANCER RESEARCH 12 ( 3 ) R43 2010

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

Introduction: Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT.
Methods: The correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT-and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes.
Results: mRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-beta-estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect.
Conclusions: Expression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT-and ER-positive breast cancer cells.

DOI： 10.1186/bcr2598

乳腺原発血管肉腫の脳転移に対して放射線治療が有効であった1例

西山慶子, 平成人, 増田紘子, 野上智弘, 杉本龍士郎, 池田宏国, 枝園忠彦, 土井原博義, 三好新一郎

日本臨床外科学会雑誌 70 ( 増刊 ) 909 - 909 2009.10

当院における乳房再建術症例の検討

増田紘子, 枝園忠彦, 西山慶子, 野上智弘, 杉本龍士郎, 池田宏国, 平成人, 元木崇之, 松岡順治, 土井原博義, 三好新一郎, 徳山英二郎, 木股敬裕

日本臨床外科学会雑誌 70 ( 増刊 ) 402 - 402 2009.10

21-Gene expression profile assay on core needle biopsies predicts responses to neoadjuvant endocrine therapy in breast cancer patients Reviewed

Sadako Akashi-Tanaka, Chikako Shimizu, Masashi Ando, Tatsuhiro Shibata, Noriyuki Katsumata, Tsutomu Kouno, Kotoe Terada, Tadahiko Shien, Miwa Yoshida, Takashi Hojo, Takayuki Kinoshita, Yasuhiro Fujiwara, Kenichi Yoshimura

BREAST 18 ( 3 ) 171 - 174 2009.6

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

This study examined postmenopausal estrogen receptor-positive breast cancer patients who received prospective neoadjuvant endocrine therapy (NAET) with tamoxifen or anastrozole to determine if the 21-gene recurrence score (RS) predicts NAET responses. RS scores were determined from pretreatment core biopsy specimens. Although half of the specimens yielded insufficient RNA, the remaining samples were highly representative. Patients with a low RS tended to respond better than those with an intermediate or high RS (n = 43). Response rates by RS were similar between the tamoxifen and anastrozole groups. Patients with a low RS tended to have better relapse-free Survival (RFS) than those with ail intermediate or high RS (5y-RFS; 100% vs. 84% and 73%, respectively). These results suggest that RS predicts responses to NAET with tamoxifen or anastrozole. Because this pilot study examined a small sample size, these results should be validated in larger studies. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.breast.2009.03.005

HER2陽性高齢者乳癌に対する術後補助療法に関するTrastuzumabと化療併用のRCT:N-SAS BC07 QOL pilot試験

平成人, 澤木正孝, 下妻晃二郎, 高橋都, 福田敬, 白岩健, 田中夕香理, 枝園忠彦, 土井原博義, 大橋靖雄

日本乳癌学会総会プログラム抄録集 17回 435 - 435 2009.6

Primary tumor resection improves the survival of younger patients with metastatic breast cancer Reviewed

Tadahiko Shien, Takayuki Kinoshita, Chikako Shimizu, Takashi Hojo, Naruto Taira, Hiroyoshi Doihara, Sadako Akashi-Tanaka

ONCOLOGY REPORTS 21 ( 3 ) 827 - 832 2009.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Current treatments for metastatic breast cancer (MBC) include palliation with chemotherapy and/or hormone therapy, neither of which has the effect of adequately improving survival. Local surgery to remove the primary breast tumor is performed to improve local control and prevent uncontrolled chest wall disease (UCD). From June 1962 to February 2007 7 344 patients with MBC were treated at National Cancer Center Hospital. In our review of these cases, we evaluated the prognostic impact of local surgery and other clinicopathological features. One hundred and sixty patients (47%) underwent resection of primary breast tumor, while 184 (53%) patients were treated without surgery. Overall survival (OS) was prolonged in patients treated with surgery (p=0.049), younger patients (age < 50, p=0.023), and patients with bone or soft tissue metastases (p=0.013). While surgery significantly improved OS in young patients (p=0.021), it did not increase OS in older patients (age > 51, p=0.665) or patients with visceral metastasis (p=0.797). This study demonstrated that local surgery improved OS of patients with MBC; local surgery should therefore be considered, especially in young patients. Prospective studies are required to validate these findings and evaluate the impact of surgical intervention.

DOI： 10.3892/or_00000291

Whole-breast volume perfusion images using 256-row multislice computed tomography: visualization of lesions with ductal spread Reviewed

Sadako Akashi-Tanaka, Tadahiko Shien, Shinsuke Tsukagoshi, Shintaro Funabasama, Kunihisa Miyagawa, Kotoe Terada, Miwa Yoshida, Takashi Hojo, Takayuki Kinoshita, Noriyuki Moriyama

BREAST CANCER 16 ( 1 ) 62 - 67 2009.1

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

Background The aim of this study was to apply perfusion techniques to breast tumors using a prototype 256-row multislice computed tomography (CT) scanner (which allows a wide range of 128 mm to be scanned and can provide whole-breast perfusion maps without any dead angles) to improve contrast and assess the possibility of precisely depicting the extent of breast cancer.
Patients and methods The study group included seven patients with breast cancer who were scheduled to undergo radical surgery and radiotherapy. Dynamic scanning was performed using a 256-row multislice CT scanner during normal respiration. Volume perfusion images of the entire breast were obtained using the maximum slope method. Perfusion map images and early-phase breast CT images at 54 s were compared by means of pathological examination.
Results All breast cancers could be distinguished from normal mammary glands based on the perfusion value. The extent of cancer depicted in perfusion images showed excellent agreement with the pathology findings for invasive ductal carcinoma and ductal carcinoma in situ. In three patients, all ductal spread, parts of which were not visualized by early-phase CT, were depicted in volume perfusion images. Simulation analysis suggested that perfusion maps could be generated with fewer scanning points.
Conclusion The results of the present study suggest that volume perfusion imaging may be useful for depicting the extent of breast cancer, with excellent sensitivity. Further research is needed to determine the clinical relevance of these findings.

DOI： 10.1007/s12282-008-0076-6

Primary small cell carcinoma of the breast Reviewed

Takashi Hojo, Takayuki Kinoshita, Tadahiko Shien, Kotoe Terada, Shigemichi Hirose, You Isobe, Shunji Ikeuchi, Kiyoshi Kubochi, Sumio Matsumoto, Akashi-Tanaka Sadako

BREAST CANCER 16 ( 1 ) 68 - 71 2009.1

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

Primary small cell carcinoma of the breast is a very rare disease, and only a few case reports have described small cell carcinoma of the breast that responds to chemotherapy. Here, we report a case of primary small cell carcinoma of the breast that was treated with surgery and chemotherapy for postoperative local recurrence in the chest wall and metastasis to the liver. The metastatic lesions showed a partial response (PR) to carboplatin and irinotecan, but did not respond to subsequent Taxotere and doxifluridine (5'-DFUR) treatment. We then treated the metastatic lesions with CBDCA and etoposide (VP-16), and were able to stop disease progression. Small cell carcinoma of the breast is as aggressive as its pulmonary counterpart. Therefore, the best therapy for primary small cell carcinoma of the breast may be surgery followed by adjuvant therapy similar to that recommended for small cell lung carcinoma.

DOI： 10.1007/s12282-008-0057-9

Usefulness of preoperative multidetector-row computed tomography in evaluating the extent of invasive lobular carcinoma in patients with or without neoadjuvant chemotherapy Reviewed

Tadahiko Shien, Sadako Akashi-Tanaka, Miwa Yoshida, Takashi Hojo, Eriko Iwamoto, Kunihisa Miyagawa, Takayuki Kinoshita

BREAST CANCER 16 ( 1 ) 30 - 36 2009.1

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

Background The present study was conducted to assess the clinical usefulness of multidetector-row CT (MDCT) in determining the extent of invasive lobular carcinoma (ILC) and especially the extent of residual tumor after neoadjuvant chemotherapy (NAC).
Patients and methods The subjects were 24 patients with primary ILC who underwent surgery without NAC and 17 patients with ILC who underwent surgery after NAC at National Cancer Center Hospital (NCCH) between April 1999 and December 2005. The extent of primary ILC was assessed by ultrasound, mammography, and MDCT before surgery, and the results obtained using each modality were compared with the results of pathological examination after surgery. In addition, the characteristic findings of ILC obtained by MDCT were assessed. Similarly, the extent of residual tumor after NAC was evaluated using ultrasound, mammography, and MDCT before surgery in the subjects who underwent NAC, and the results obtained by each modality were compared with the results of pathological examination after surgery.
Results The findings of primary ILC obtained by MDCT showed that the carcinoma was the non-localized type rather than the localized type in 63% of the subjects. In addition, with regard to the pattern of time-sequential contrast enhancement, the persistent pattern (in which tumor enhancement is strong in the late phase rather than in the early phase) was observed in 46% of the subjects, and the plateau pattern (in which contrast enhancement is weak in both the early phase and the late phase) was observed in 38% of the subjects. These trends were significant in the subjects who underwent NAC and in whom tumor enhancement could not be clearly observed by MDCT. Assessment of the extent of carcinoma showed that the diagnostic accuracy of MDCT was 79%, as compared with 71% for either ultrasound or mammography. Assessment of the extent of carcinoma after NAC also showed that the diagnostic accuracy of MDCT was 71%, as compared with 48% for ultrasound and 53% for mammography, indicating that MDCT provided the highest accuracy. It should be noted that for all modalities, the extent of ILC was not overestimated as compared with the tumor diameter measured during pathological examination.
Conclusion Assessment by MDCT showed that ILC tends to be diffuse, tumor enhancement tends to be very weak, and the rate of enhancement tends to be low. In addition, MDCT was found to be useful for determining the extent of carcinoma, and the diagnostic accuracy of MDCT, especially in determining the extent of carcinoma after NAC, was much higher than that of ultrasound or mammography.

DOI： 10.1007/s12282-008-0044-1

Comparison among different classification systems regarding the pathological response of preoperative chemotherapy in relation to the long-term outcome Reviewed

Tadahiko Shien, Chikako Shimizu, Kunihiko Seki, Taro Shibata, Takashi Hojo, Masashi Ando, Tsutomu Kohno, Noriyuki Katsumata, Sadako Akashi-Tanaka, Takayuki Kinoshita, Yasuhiro Fujiwara

BREAST CANCER RESEARCH AND TREATMENT 113 ( 2 ) 307 - 313 2009.1

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

Neoadjuvant chemotherapy (NAC) is increasingly used for operable disease. However there are several pathological response classification systems and the correlation between the pathological response to NAC according to each system and the patient outcome is still under debate. From 1998 to 2006, 370 primary breast cancer patients underwent curative surgical treatment after NAC containing both anthracycline and taxane at the National Cancer Center Hospital. We retrospectively evaluated the clinical and pathological response using the cTMN, Fisher's, Chevailler's, and the Japanese Breast Cancer Society classification systems (JBCS) respectively, and analyzed the correlation between each pathological response and disease free survival (DFS). Ninety-five (26%) patients had tumor recurrence. The five-year DFS according to Fisher's system was pCR, 80% and pINV, 63%. The five-year DFS according to Chevallier's system was Grade 1, 83%, Grade 2, 85%, Grade 3, 62%, and Grade 4, 65%. The five-year DFS according to the JBSC system was Grade 3, 77%, Grade 2, 68%, Grade 1a, 68%, Grade 1b, 58%, and Grade 0, 52%. None of the pathological response systems reached a statistically significant difference. In the classification by the post-treatment number of metastatic axillary lymph nodes, the 5-year DFS was n = 0, 86%; n = 1-3, 64%; n = 4-9, 44%; and n > 10 positive: 25% (P < .0001). In pathologically node negative patients, there were no significant differences in the DFS among all the classification systems. All three classifications analyzed were considered inadequate as the prognostic marker of the long-term outcome after NAC and further studies are warranted to optimize the prediction.

DOI： 10.1007/s10549-008-9935-2

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