Faculty Profiles - SHIEN Tadahiko

Papers - SHIEN Tadahiko

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転移再発乳癌におけるがんゲノムプロファイリングの現状と問題点がん遺伝子パネル検査の前向き観察研究(REIWA study)の中間解析結果と乳癌ゲノム医療の問題点

多田寛, 増田紘子, 安立弥生, 岩谷胤生, 上本康明, 大谷陽子, 梶原友紀子, 北川大, 古川孝広, 相良安昭, 枝園忠彦, 田辺裕子, 谷岡真樹, 原文堅, 八十島宏行, 服部正也, 吉村健一, 岩田広治, 増田慎三

日本乳癌学会総会プログラム抄録集 32回 25 - 25 2024.7

多様な背景を持つ乳癌患者の意思決定支援 LGBTに対する乳癌診療の事例報告

枝園忠彦, 染田朋子, 露無祐子, 三又明日香, 間森智花, 中本翔吾, 岩谷陽子, 突沖貴宏, 高橋侑子, 岩谷胤生, 谷岡真樹

日本乳癌学会総会プログラム抄録集 32回 29 - 29 2024.7

乳房部分切除後の温存乳房内再発時の手術術式選択に関する患者意向について

瀬戸友希子, 石飛真人, 枝園忠彦, 大城智弥, 井上寛章, 島宏彰, 久芳さやか, 渡邉法之, 岩谷胤生, 中山貴寛

日本乳癌学会総会プログラム抄録集 32回 261 - 261 2024.7

BRCA病的バリアントを有する乳癌患者における術前化学療法に対する治療奏効率の検討

三又明日香, 高橋侑子, 中本翔伍, 突沖貴宏, 岩谷陽子, 谷岡真樹, 岩谷胤生, 枝園忠彦

日本乳癌学会総会プログラム抄録集 32回 289 - 289 2024.7

術前薬物療法後病理学的完全奏効到達症例における早期遠隔再発症例の検討

高橋侑子, 三又明日香, 中本翔伍, 岩谷陽子, 突沖貴宏, 谷岡真樹, 岩谷胤生, 枝園忠彦

日本乳癌学会総会プログラム抄録集 32回 297 - 297 2024.7

当院における乳腺葉状腫瘍の正診率と再発率の検討

中本翔伍, 突沖貴宏, 三又明日香, 高橋侑子, 岩谷陽子, 岩谷胤生, 谷岡真樹, 枝園忠彦

日本乳癌学会総会プログラム抄録集 32回 407 - 407 2024.7

重篤な薬剤性心不全にて長期入院加療を要した2症例の検討

間森智加, 突沖貴宏, 三又明日香, 中本翔伍, 岩谷陽子, 高橋侑子, 谷岡真樹, 岩谷胤生, 枝園忠彦

日本乳癌学会総会プログラム抄録集 32回 480 - 480 2024.7

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306. Reviewed International journal

Tadahiko Shien, Hitoshi Tsuda, Keita Sasaki, Junki Mizusawa, Futoshi Akiyama, Masafumi Kurosumi, Masataka Sawaki, Nobuko Tamura, Kiyo Tanaka, Takahiro Kogawa, Mina Takahashi, Naoki Hayashi, Hirofumi Mukai, Norikazu Masuda, Fumikata Hara, Hiroji Iwata

Breast cancer research and treatment 2024.6

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. METHODS: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. RESULTS: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. CONCLUSIONS: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

DOI： 10.1007/s10549-024-07408-5

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Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project-14. Reviewed International journal

Shogo Nakamoto, Yukiko Kajiwara, Kohei Taniguchi, Akira I Hida, Yuichiro Miyoshi, Takanori Kin, Mari Yamamoto, Daisuke Takabatake, Shinichiro Kubo, Hajime Hikino, Yutaka Ogasawara, Masahiko Ikeda, Hiroyoshi Doihara, Tadahiko Shien, Naruto Taira, Takayuki Iwamoto, Shinichi Toyooka

Breast cancer research and treatment 2024.6

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

PURPOSE: Various studies have demonstrated the causal relationship between gut microbiota and efficacy of chemotherapy; however, the impact of gut microbiota on breast cancer has not been fully elucidated. This study aimed to evaluate the associations between the gut microbiota before neoadjuvant chemotherapy and its consequent efficacy in breast cancer. METHODS: This prospective observational study included patients who received neoadjuvant chemotherapy for primary early breast cancer at eight institutions between October 1, 2019, and March 31, 2022. We performed 16S rRNA analysis of fecal samples and α and β diversity analyses of the gut microbiota. The primary endpoint was the association between the gut microbiota and pathological complete response (pCR) to neoadjuvant chemotherapy. RESULTS: Among the 183 patients, the pCR rate after neoadjuvant chemotherapy was 36.1% in all patients and 12.9% (9/70), 69.5% (41/59), and 29.6% (16/54) in those with the luminal, human epidermal growth factor receptor 2, and triple-negative types, respectively. The α diversity of the gut microbiota did not significantly differ between patients with pCR and those without pCR. Among the gut microbiota, two species (Victivallales, P = 0.001 and Anaerolineales, P = 0.001) were associated with pCR, and one (Gemellales, P = 0.002) was associated with non-pCR. CONCLUSION: Three species in the gut microbiota had potential associations with neoadjuvant chemotherapy efficacy, but the diversity of the gut microbiota was not associated with response to chemotherapy. Further research is needed to validate our findings.

DOI： 10.1007/s10549-024-07395-7

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Impact of radiation therapy for breast cancer with involved surgical margin after immediate breast reconstruction: A multi-institutional observational study. Reviewed International journal

Shinsuke Sasada, Naomi Nagura, Ayaka Shimo, Akiko Ogiya, Miho Saiga, Hirohito Seki, Hiroki Mori, Naoto Kondo, Makoto Ishitobi, Kazutaka Narui, Hiroko Nogi, Chikako Yamauchi, Teruhisa Sakurai, Tadahiko Shien

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 50 ( 6 ) 108360 - 108360 2024.6

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Involved surgical margins are risk factors for local recurrence and re-excision is often difficult, particularly in patients with breast cancer undergoing immediate breast reconstruction (IBR). However, the magnitude of the effect of radiation therapy on preventing local recurrence for breast cancers with involved margins has not been sufficiently assessed. MATERIALS AND METHODS: We retrospectively assessed sites of involved surgical margins and local recurrence after mastectomy with IBR in patients with early breast cancer between 2008 and 2016. The effect of postoperative radiation therapy was evaluated in patients with involved margins, adjusted for nuclear grade, lymphatic invasion, surgical procedures, and primary systemic therapy. RESULTS: A total of 274 (5.8 %) out of 4726 patients who underwent mastectomy with IBR had involved surgical margins: 133, 68, 88, and 26 had involvement of the skin, deep margin, lateral margins, and nipple, respectively (including duplicates). Radiation therapy was administered to 54 patients with involved margins. In patients with involved margins, 7-year cumulative incidences of local recurrence were 1.9 % and 12.6 % with and without radiation therapy, respectively (adjusted hazard ratio, 0.17; 95 % CI, 0.04-0.80). Local recurrence occurred in 28 patients, and the sites were skin, subcutaneous tissue, muscle, and nipple-areola complex in 7, 17, 1, and 3 patients, respectively. Among them, 23 (82.1 %) were associated with involved margin sites. CONCLUSIONS: Radiation therapy meaningfully reduced the incidence of local recurrence in patients with breast cancer with margin involvement after mastectomy with IBR. Most local recurrences occurred at involved margin-related sites.

DOI： 10.1016/j.ejso.2024.108360

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Receptor discordance after nipple-sparing mastectomy. International journal

Rena Kojima, Makoto Ishitobi, Naomi Nagura, Ayaka Shimo, Hirohito Seki, Akiko Ogiya, Teruhisa Sakurai, Yukiko Seto, Shinsuke Sasada, Chiya Oshiro, Michiko Kato, Takahiko Kawate, Naoto Kondo, Tadahiko Shien

Surgery in practice and science 17 100239 - 100239 2024.6

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

BACKGROUND: Recent studies have shown that receptor status of breast cancer change between primary tumor and recurrence, which may influence treatment strategy and prognosis, but there are few reports on receptor discordance between primary tumors and local recurrence (LR) after nipple-sparing mastectomy (NSM). PATIENTS AND METHODS: We collected 74 patients who had LR after NSM for newly diagnosed stages 0 to 3 breast cancer between 2008 and 2016 at 14 institutions. We classified into 4 subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). We evaluated clinicopathological factors that correlate with receptor discordance and assessed the impact of receptor discordance on survival. RESULTS: Discordance rates in estrogen receptor (ER), progesterone receptor (PgR) and HER2 were 9.5, 10.8 and 5.4 %, respectively. The most common change was from HR-/HER2+ to HR+/HER2+, and this pattern of receptor change occurred only in patients with nipple-areolar recurrence. Non-invasive tumors in LR, nipple-areolar recurrence (NAR), HR-/HER2+ primary tumor subtype, and the presence of chemotherapy for primary tumors were significantly associated with receptor discordance. With a median follow-up of 44.5 months (4-153 months), patients in the receptor-discordant group had no disease-free survival (DFS) event after LR resection (5-year DFS; 100 % in the receptor-discordant group vs 85.1 % in the receptor-concordant group; p = 0.2). CONCLUSION: Our study demonstrates that the presence of chemotherapy for primary tumors, nipple-areolar recurrence, and its related factors (non-invasive tumor in LR, HR-/HER2+ primary tumor subtype) were associated with receptor discordance. However, further studies with longer follow-up periods and larger sample sizes are needed.

DOI： 10.1016/j.sipas.2024.100239

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The specific shapes of capillaries are associated with worse prognosis in patients with invasive breast cancer. Reviewed International journal

Hnin-Wint-Wint Swe, Masayoshi Fujisawa, Toshiaki Ohara, Yu Komatsubara, Teizo Yoshimura, Tadahiko Shien, Akihiro Matsukawa

Pathology international 2024.5

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

Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) is associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined based on the MVD value, and the presence of GMP and other blood vessels with other specific shapes. As a result, high MVD value and the presence of GMP were not associated with worse prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index. Thus, the morphology of capillaries rather than MVD can be a better indicator of tumor aggressiveness.

DOI： 10.1111/pin.13442

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ASO Visual Abstract: Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence. Reviewed International journal

Yukiko Seto, Makoto Ishitobi, Tadahiko Shien, Chiya Oshiro, Hiroaki Inoue, Hiroaki Shima, Sayaka Kuba, Noriyuki Watanabe, Tsuguo Iwatani, Takahiro Nakayama

Annals of surgical oncology 2024.5

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy. Reviewed

Hiroko Nogi, Akiko Ogiya, Makoto Ishitobi, Chikako Yamauchi, Hiroki Mori, Ayaka Shimo, Kazutaka Narui, Naomi Nagura, Hirohito Seki, Shinsuke Sasada, Teruhisa Sakurai, Tadahiko Shien

Breast cancer (Tokyo, Japan) 31 ( 3 ) 507 - 518 2024.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR. METHODS: This was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival. RESULTS: Of the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74-1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups. CONCLUSION: IBR after NAC is a safe procedure with an acceptable postoperative complication profile.

DOI： 10.1007/s12282-024-01570-w

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Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer. Reviewed International journal

Shogo Nakamoto, Tadahiko Shien, Takayuki Iwamoto, Shinichiro Kubo, Mari Yamamoto, Tetsumasa Yamashita, Chihiro Kuwahara, Masahiko Ikeda

Scientific reports 14 ( 1 ) 9869 - 9869 2024.4

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

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/μL for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC.

DOI： 10.1038/s41598-024-60101-x

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Adrenergic microenvironment driven by cancer-associated Schwann cells contributes to chemoresistance in patients with lung cancer. Reviewed International journal

Yusuke Otani, Haruyoshi Katayama, Yidan Zhu, Rongsheng Huang, Takafumi Shigehira, Kazuhiko Shien, Ken Suzawa, Hiromasa Yamamoto, Tadahiko Shien, Shinichi Toyooka, Atsushi Fujimura

Cancer science 2024.4

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

Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.

DOI： 10.1111/cas.16164

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Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence. Reviewed International journal

Yukiko Seto, Makoto Ishitobi, Tadahiko Shien, Chiya Oshiro, Hiroaki Inoue, Hiroaki Shima, Sayaka Kuba, Noriyuki Watanabe, Tsuguo Iwatani, Takahiro Nakayama

Annals of surgical oncology 2024.4

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

BACKGROUND: Mastectomy has been the standard surgical treatment for ipsilateral breast tumor recurrence (IBTR). Recently, there has been growing interest in repeat breast-conserving surgery (rBCS) for IBTR among breast surgeons; however, there is currently little information regarding patient preferences for surgical procedure for IBTR. The purpose of this study was to evaluate preference for surgical procedure (mastectomy vs. rBCS) among breast cancer patients who had undergone salvage surgery for IBTR. METHODS: Overall, 100 breast cancer patients who had undergone salvage surgery for IBTR were asked about their preferred surgical methods for IBTR and the reason. The association of patient preference and the reasons related to various clinical and pathological factors were assessed. RESULTS: Of the 100 respondents, only 11 patients (11%) preferred rBCS. Patients who had undergone rBCS and radiotherapy for IBTR were significantly more likely to prefer to undergo rBCS than other groups (p = 0.030). The most frequent reason for choosing rBCS was the patient's desire to minimize breast deformity and surgical wounds. CONCLUSIONS: Our study revealed that there is a low rate of patients who opt to undergo rBCS among patients who had undergone salvage surgery for IBTR. Discrepancies in perceptions regarding the surgical procedure for IBTR between patients and their surgeons may exist.

DOI： 10.1245/s10434-024-15282-0

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乳癌領域外科治療の個別化 de-novo Stage IV乳がんに対する原発巣切除について残されたCQと次の展開

枝園忠彦, 岡美苗, 中山恵利香, 三又明日香, 桑原ちひろ, 間森智加, 中本翔吾, 突沖貴宏, 高橋侑子, 岩谷胤生

日本外科学会定期学術集会抄録集 124回 WS - 7 2024.4

内分泌外科領域における米国式手術手技評価法を用いた専門医養成の取り組み Operative Performance Rating Scale日本語版の作成

岩谷胤生, 突沖貴宏, 高橋侑子, 枝園忠彦

日本内分泌外科学会雑誌 41 ( Suppl.1 ) S204 - S204 2024.4

内分泌外科領域における米国式手術手技評価法を用いた専門医養成の取り組み Operative Performance Rating Scale日本語版の作成

岩谷胤生, 突沖貴宏, 高橋侑子, 枝園忠彦

日本内分泌外科学会雑誌 41 ( Suppl.1 ) S204 - S204 2024.4

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Papers - SHIEN Tadahiko