Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes
Hiroko Masuda,Keith A. Baggerly,Ying Wang,Ya Zhang,Ana M. Gonzalez-Angulo,Funda Meric-Bernstam,Vicente Valero,Brian D. Lehmann,Jennifer A. Pietenpol,Gabriel N. Hortobagyi,W. Fraser Symmans,Naoto T. Ueno +11 more
TLDR
The clinical relevancy of the 7-subtype classification of triple-negative breast cancer reported by Lehmann and colleagues is confirmed, and may spur innovative personalized medicine strategies for patients with TNBC.Abstract:
Purpose: The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based on TNBC subtypes. Experimental Design: We revalidated the Lehmann and colleagues experiments using Affymetrix CEL files from public datasets. We applied these methods to 146 patients with TNBC with gene expression microarrays obtained from June 2000 to March 2010 at our institution. Of those, 130 had received standard neoadjuvant chemotherapy and had evaluable pathologic response data. We classified the TNBC samples by subtype and then correlated subtype and pCR status using Fisher exact test and a logistic regression model. We also assessed survival and compared the subtypes with PAM50 intrinsic subtypes and residual cancer burden (RCB) index. Results: TNBC subtype and pCR status were significantly associated ( P = 0.04379). The basal-like 1 (BL1) subtype had the highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor had the lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of pCR status ( P = 0.022) by a likelihood ratio test. The subtypes better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like). Conclusions: Classifying TNBC by 7 subtypes predicts high versus low pCR rate. We confirm the clinical relevancy of the 7 subtypes of TNBC. We need to prospectively validate whether the pCR rate differences translate into long-term outcome differences. The 7-subtype classification may spur innovative personalized medicine strategies for patients with TNBC. Clin Cancer Res; 19(19); 5533–40. ©2013 AACR .read more
Citations
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Gene regulatory pattern analysis reveals essential role of core transcriptional factors' activation in triple-negative breast cancer.
Li Min,Li Min,Cheng Zhang,Like Qu,Jialiang Huang,Lan Jiang,Jiafei Liu,Luca Pinello,Guo-Cheng Yuan,Chengchao Shou +9 more
TL;DR: A core co-regulatory module specifically existing in TNBC enabled subtype re-classification and provided a biologically feasible view of breast cancer.
Journal ArticleDOI
Sequential combination of docetaxel with a SHP-1 agonist enhanced suppression of p-STAT3 signaling and apoptosis in triple negative breast cancer cells
Chunyu Liu,Chunyu Liu,Kuen-Feng Chen,Tzu I. Chao,Pei-Yi Chu,Pei-Yi Chu,Chun Teng Huang,Tzu Ting Huang,Hsiu Ping Yang,Wan-Lun Wang,Chia Han Lee,Ka Yi Lau,Wen Chun Tsai,Jung Chen Su,Chia Yun Wu,Chia Yun Wu,Ming Huang Chen,Ming Huang Chen,Chung Wai Shiau,Ling Ming Tseng,Ling Ming Tseng +20 more
TL;DR: The results suggest that the novel SHP-1 agonist SC-43 enhanced docetaxel-induced cytotoxicity by SHp-1 dependent STAT3 inhibition in human triple negative breast cancer cells.
Journal ArticleDOI
Role of Platinum in Early-Stage Triple-Negative Breast Cancer.
TL;DR: The role of platinums in the treatment of TNBC, as well as the potential for biomarkers to predict patient response to these agents, are explored, with no evidence yet that these agents would lead to improvement in disease-free and overall survival.
Journal ArticleDOI
Pathological features of triple-negative breast cancers that showed progressive disease during neoadjuvant chemotherapy
Yuko Tanabe,Hitoshi Tsuda,Masayuki Yoshida,Mayu Yunokawa,Kan Yonemori,Chikako Shimizu,Seiichiro Yamamoto,Takayuki Kinoshita,Yasuhiro Fujiwara,Kenji Tamura +9 more
TL;DR: The combinations of high proliferation, metaplastic features, and immunohistochemical statuses of some EMT and basal‐like markers and androgen receptor appeared to be able to characterize the TNBCs that showed cPD after NAC.
Journal ArticleDOI
Recent advances in understanding breast cancer and emerging therapies with a focus on luminal and triple-negative breast cancer
TL;DR: The options are still limited for triple-negative breast cancer, but the better knowledge of its complex biology and the discovery of molecular targets are promising for more efficient novel therapies.
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