Molecular Characterization of Basal-Like and Non-Basal-Like Triple-Negative Breast Cancer
TLDR
The results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.Abstract:
Triple-negative (TN) and basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormone receptors and overexpression and/or amplification of HER2. However, both classifications show substantial discordance rates when compared to each other. Here, we molecularly characterize TN tumors and BL tumors, comparing and contrasting the results in terms of common patterns and distinct patterns for each. In total, when testing 412 TN and 473 BL tumors, 21.4% and 31.5% were identified as non-BL and non-TN, respectively. TN tumors identified as luminal or HER2-enriched (HER2E) showed undistinguishable overall gene expression profiles when compared versus luminal or HER2E tumors that were not TN. Similar findings were observed within BL tumors regardless of their TN status, which suggests that molecular subtype is preserved regardless of individual marker results. Interestingly, most TN tumors identified as HER2E showed low HER2 expression and lacked HER2 amplification, despite the similar overall gene expression profiles to HER2E tumors that were clinically HER2-positive. Lastly, additional genomic classifications were examined within TN and BL cancers, most of which were highly concordant with tumor intrinsic subtype. These results suggest that future clinical trials focused on TN disease should consider stratifying patients based upon BL versus non-BL gene expression profiles, which appears to be the main biological difference seen in patients with TN breast cancer.read more
Citations
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Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
TL;DR: The most relevant molecular findings in TNBC from the past decade are discussed and the most promising therapeutic opportunities derived from these data are discussed.
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Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015
Alan S. Coates,Eric P. Winer,A. Goldhirsch,Richard D. Gelber,Michael Gnant,Martine Piccart-Gebhart,Beat Thürlimann,H.-J. Senn +7 more
TL;DR: The 14th St Gallen International Breast Cancer Conference (2015) reviewed new evidence on locoregional and systemic therapies for early breast cancer and summarizes treatment-oriented classification of subgroups and treatment recommendations.
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Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin
Katherine A. Hoadley,Christina Yau,Denise M. Wolf,Andrew D. Cherniack,David Tamborero,Sam Ng,Max D M Leiserson,Beifang Niu,Michael D. McLellan,Vladislav Uzunangelov,Jiashan Zhang,Cyriac Kandoth,Rehan Akbani,Hui Shen,Larsson Omberg,Andy Chu,Adam A. Margolin,Laura J. van't Veer,Nuria Lopez-Bigas,Nuria Lopez-Bigas,Peter W. Laird,Benjamin J. Raphael,Li Ding,A. Gordon Robertson,Lauren Averett Byers,Gordon B. Mills,John N. Weinstein,Carter Van Waes,Zhong Chen,Eric A. Collisson,Christopher C. Benz,Charles M. Perou,Joshua M. Stuart +32 more
TL;DR: An integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types revealed a unified classification into 11 major subtypes, revealing several distinct cancer types found to converge into common subtypes.
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Comprehensive Genomic Analysis Identifies Novel Subtypes and Targets of Triple-Negative Breast Cancer
Matthew D. Burstein,Anna Tsimelzon,Graham M. Poage,Kyle R. Covington,Alejandro Contreras,Suzanne A. W. Fuqua,Michelle I. Savage,C. Kent Osborne,Susan G. Hilsenbeck,Jenny C. Chang,Gordon B. Mills,Ching C. Lau,Powel H. Brown +12 more
TL;DR: There are four stable TNBC subtypes characterized by the expression of distinct molecular profiles that have distinct prognoses, and novel subtype-specific targets that can be targeted in the future for the effective treatment of TNBCs are identified.
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Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)
William M. Sikov,Donald A. Berry,Charles M. Perou,Baljit Singh,Constance Cirrincione,Sara M. Tolaney,Charles S. Kuzma,Timothy J. Pluard,George Somlo,Elisa Port,Mehra Golshan,Jennifer R. Bellon,Deborah Collyar,Olwen Hahn,Lisa A. Carey,Clifford A. Hudis,Eric P. Winer +16 more
TL;DR: In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown.
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