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
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Predicting response and survival in chemotherapy-treated triple-negative breast cancer.
Aleix Prat,A. Lluch,Joan Albanell,William T. Barry,Chun-Yang Fan,Jose Ignacio Chacon,Joel S. Parker,Lourdes Calvo,Arrate Plazaola,A. Arcusa,Miguel Angel Seguí-Palmer,Octavio Burgues,Nuria Ribelles,Álvaro Rodríguez-Lescure,Ángel L Guerrero,Manuel Ruiz-Borrego,Blanca Munárriz,José A. López,Barbara Adamo,Maggie C.U. Cheang,Yufeng Li,Zhiyuan Hu,Margaret L. Gulley,Maria Vidal,Brandy Pitcher,MC Liu,Marc L. Citron,Matthew J. Ellis,Elaine R. Mardis,Tammi L. Vickery,Clifford A. Hudis,Eric P. Winer,Lisa A. Carey,Rafael Caballero,Eva Carrasco,Miguel Martin,Charles M. Perou,E. Alba +37 more
TL;DR: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.
Journal ArticleDOI
miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer.
TL;DR: The data suggest that miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis and may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.
Journal ArticleDOI
Patient similarity for precision medicine: A systematic review
TL;DR: The present review investigates the use of patient similarity as a tool to enable precision medicine and finds that cancer-related research employing molecular profiling and standard data analysis techniques such as clustering constitute the majority of the retrieved studies.
Journal ArticleDOI
Androgen Receptor Biology in Triple Negative Breast Cancer: a Case for Classification as AR+ or Quadruple Negative Disease
Valerie N. Barton,Nicholas C. D'Amato,Michael A. Gordon,Jessica L. Christenson,Anthony D. Elias,Jennifer K. Richer +5 more
TL;DR: It is proposed that TNBC be further sub-classified as either AR+ TNBC or quadruple negative breast cancer since targeting AR may represent a viable therapeutic option for a subset of TNBC.
Journal Article
miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN
TL;DR: MiR-21 was upregulated in TNBC tissues and cells, and promoted the proliferation and invasion of MDA-MB-468 cells, but negatively regulated the expression of PTEN protein, indicating that PTEN may mediate the oncogenic properties of miR- 21 in T NBC.
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