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: 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.
Journal ArticleDOI
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.
Journal ArticleDOI
Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection
Brian D. Lehmann,Bojana Jovanovic,Xi Chen,Monica V. Estrada,Kimberly N. Johnson,Yu Shyr,Harold L. Moses,Melinda E. Sanders,Jennifer A. Pietenpol +8 more
TL;DR: Pre-clinical data is provided that could inform clinical trials designed to test the hypothesis that improved outcomes can be achieved for TNBC patients, if selection and combination of existing chemotherapies is directed by knowledge of molecular TNBC subtypes.
Journal ArticleDOI
Triple-negative breast cancer molecular subtyping and treatment progress.
TL;DR: This paper aims to provide new ideas for TNBC treatment by summarizing existing treatment regimens, therapeutic drugs, and their efficacy for different TNBC subtypes and reviewing some new preclinical studies and targeted treatment regimen for T NBC.
Journal ArticleDOI
Clinical implications of the intrinsic molecular subtypes of breast cancer.
Aleix Prat,Aleix Prat,Estela Pineda,Barbara Adamo,Barbara Adamo,Patricia Galván,Aranzazu Fernandez,Aranzazu Fernandez,Lydia Gaba,Lydia Gaba,Marc Díez,Marc Díez,Margarita Viladot,Margarita Viladot,Ana Arance,Ana Arance,Montserrat Muñoz,Montserrat Muñoz +17 more
TL;DR: Data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications within triple-negative breast cancer (TNBC) and within hormone receptor-positive and HER2-negative early breast cancer.
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Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy
W. Fraser Symmans,Florentia Peintinger,Christos Hatzis,Radhika Rajan,Henry Mark Kuerer,Vicente Valero,Lina Assad,Anna Poniecka,Bryan T. Hennessy,Marjorie C. Green,Aman U. Buzdar,S. Eva Singletary,Gabriel N. Hortobagyi,Lajos Pusztai +13 more
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Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer
Kenneth R. Hess,Keith Anderson,W. Fraser Symmans,Vicente Valero,Nuhad K. Ibrahim,Jaime A. Mejia,Daniel J. Booser,Richard L. Theriault,Aman U. Buzdar,Peter J. Dempsey,Roman Rouzier,Nour Sneige,Jeffrey S. Ross,Tatiana Vidaurre,Henry L. Gomez,Gabriel N. Hortobagyi,Lajos Pusztai +16 more
TL;DR: A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value.
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