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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Targeting Different Pathways Using Novel Combination Therapy in Triple Negative Breast Cancer.
TL;DR: Light is shed on the novel combinatorial approaches targeting PARP, EGFR, PI3K pathway, AR, and wnt signaling, HDAC, MEK pathway for efficient treatment of high-grade tumors like TNBC and decreasing the onset of resistance.
Journal ArticleDOI
Targeting the androgen receptor in triple-negative breast cancer: current perspectives
TL;DR: As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition.
Journal ArticleDOI
BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential
Tesa M. Severson,J. Peeters,Ian J. Majewski,Magali Michaut,Astrid Bosma,Philip C. Schouten,Suet-Feung Chin,Bernard Pereira,Mae A. Goldgraben,Tycho Bismeijer,Roelof J.C. Kluin,Jettie J.F. Muris,Karin Jirström,Ron M. Kerkhoven,Lodewyk F. A. Wessels,Carlos Caldas,René Bernards,Iris Simon,Sabine C. Linn,Sabine C. Linn +19 more
TL;DR: A significant association with worse prognosis was evident for patients with BRCA1‐like tumors, and subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors.
Journal ArticleDOI
Tumor Sequencing and Patient-Derived Xenografts in the Neoadjuvant Treatment of Breast Cancer
Matthew P. Goetz,Krishna R. Kalari,Vera J. Suman,Ann M. Moyer,Jia Yu,Daniel W. Visscher,Travis J. Dockter,Peter T. Vedell,Jason P. Sinnwell,Xiaojia Tang,Kevin J. Thompson,Sarah A. McLaughlin,Alvaro Moreno-Aspitia,John A. Copland,Donald W. Northfelt,Richard Gray,Katie N. Hunt,Amy Lynn Conners,Hugues Sicotte,Jeanette E. Eckel-Passow,Jean-Pierre A. Kocher,James N. Ingle,Marissa S. Ellingson,Michelle McDonough,Eric D. Wieben,Richard M. Weinshilboum,Liewei Wang,Judy C. Boughey +27 more
TL;DR: The feasibility of tumor sequencing and PDX generation in the NAC setting is demonstrated and prioritization of drug testing based on sequence data may accelerate drug development.
Journal ArticleDOI
Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway.
Han-Tsang Wu,Joseph Lin,Yi-En Liu,Hsiao-Fan Chen,Kai-Wen Hsu,Shu-Hsuan Lin,Kai-Yen Peng,Kuo-Juei Lin,Chang-Chi Hsieh,Dar-Ren Chen +9 more
TL;DR: It is indicated that luteolin inhibited the proliferation and metastasis of androgen receptor-positive TNBC by regulating MMP9 expression through a reduction in the levels of AKT/mTOR-inducing H3K27Ac and H3k56Ac.
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