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
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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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Triple-negative breast cancer and the potential for targeted therapy.
Jing Ru Jhan,Eran R. Andrechek +1 more
TL;DR: This review summarizes studies of targeted therapy, including within mouse models, and discusses their applications in the development of combinatorial treatments to treat TNBC.
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Molecular classification of breast cancer
TL;DR: There are now genome-based frameworks for the molecular categorisation of breast cancer including the development of prognostic and predictive signatures that potentially allow individualisation of treatment.
Journal ArticleDOI
Recent therapeutic trends and promising targets in triple negative breast cancer.
TL;DR: The complicated tumorigenic processes are reviewed and critical findings and therapeutic trends in TNBC are discussed with a focus on promising therapeutic approaches, the clinical trials currently underway, and potent experimental compounds under preclinical and evaluation.
Journal ArticleDOI
Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies
Mauricio A. Medina,Goldie Oza,Ashutosh Sharma,Luis Gerardo Arriaga,José Manuel Hernández,Vincent M. Rotello,Jose Tapia Ramirez +6 more
TL;DR: The resistance of TNBC to conventional therapeutic agents has helped in the advancement of advanced TNBC therapeutic approaches including hyperthermia, photodynamic therapy, as well as nanomedicine-based targeted therapeutics of drugs, miRNA, siRNA, and aptamers, which will also be discussed.
Journal ArticleDOI
Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies.
Gagan K. Gupta,Amber L. Collier,Dasom Lee,Richard A. Hoefer,Vasilena Zheleva,Lauren L. Siewertsz van Reesema,Angela M. Tang-Tan,Mary L. Guye,David Z. Chang,Janet S. Winston,Billur Samli,Rick J. Jansen,Emanuel F. Petricoin,Matthew P. Goetz,Harry D. Bear,Amy H. Tang +15 more
TL;DR: It is proposed that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumors vulnerability in TNBC.
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