ドイハラ ヒロヨシ   Hiroyoshi Doihara
  土井原 博義
   所属   川崎医科大学  医学部 臨床医学 総合外科学
   職種   特任教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Tumour-infiltrating lymphocytes (TILs)-related genomic signature predicts chemotherapy response in breast cancer.
掲載誌名 正式名:Breast cancer research and treatment
略  称:Breast Cancer Res Treat
ISSNコード:15737217/01676806
掲載区分国外
巻・号・頁 167(1),pp.39-47
著者・共著者 Kochi Mariko, Iwamoto Takayuki, Niikura Naoki, Bianchini Giampaolo, Masuda Shinobu, Mizoo Taeko, Nogami Tomohiro, Shien Tadahiko, Motoki Takayuki, Taira Naruto, Tokuda Yutaka, Doihara Hiroyoshi, Matsuoka Junji, Fujiwara Toshiyoshi
発行年月 2018/01
概要 PURPOSE:The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes.METHODS:We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies.RESULTS:Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P < 0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95% CI 1.30-3.14, P = 0.025).CONCLUSIONS:TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes.
DOI 10.1007/s10549-017-4502-3
PMID 28905250