Gene Signatures as predictors of response to neoadjuvant chemotherapy with docetaxel, doxorubicin, cyclophosphamide (TAC), or AC and nab-paclitaxel and carboplatin +/- trastuzumab in patients with stage II-III and inflammatory breast cancer.

Publication Name: ASCO Poster 2010

Author(s): G. Somlo, P. H. Frankel, L. Vora, S. Lau, T. H. Luu, L. Kruper, J. Yim, Y. Yen, F. de Snoo, R. A. Bender

Pathologic complete response (pCR) and residual cancer burden (RCB) scores of 0 (pCR) and 1 (near CR) after NCT predict for better survival (Symmans et al. J Clin Oncol 25:4414-22, 2007). Improved NCTs and molecular markers predicting for response are needed. Methods: Pts with HER2- BC were randomized to receive 6 cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (TAC, Arm A) versus A 60 mg/m2 and C 600 mg/m2 given every 2 weeks x 4, followed by 3 weekly doses of carboplatin (carbo) at an AUC 2,and nab- P 100 mg/m2, repeated as 28 day cycles x 3 ( Arm B). Pts with HER2+ BC (by immunohistochemistry [IHC] and/or FISH) received NCT as per Arm B, but, with trastuzumab (trast) given weekly with carbo and nab (Arm C). Core biopsies were taken pre-NCT. 70-gene (MammaPrint) profiling for poor vs. good risk features, and 80-gene profiling for basal, HER2+, and luminal subtypes were performed. We assessed the predictive value of gene profiling for response to NCT, as a function of RCB scores of 0-1 vs. > 1. Results: Pre-NCT fresh tissue was procured from 97 pts. Pts were treated for stage II (49%), III (locally advanced [51%] and IBC [16%]) BC; 57% of BCs were ER and/or PR+ and 36% were HER2+ (by IHC/or FISH). RCB scores were available in 90% of pts enrolled (10% is awaiting surgery): scores of 0-1 were observed in 29% pts treated on either Arms A or B, and in 64% of pts treated on Arm C. There was 98% concordance of HER2- BCs by IHC/FISH vs. gene profiling; 35% of HER2+ BCs by IHC/FISH were HER2- by gene profiling. Of the 25 pts with response data on Arm C, 8 of 19 pts who were HER2+ by both IHC/FISH and HER2+ gene profiling, achieved pCR (RCB 0), vs. 2 of 6 pts with HER2+ BC by IHC/FISH, but with HER2- gene profiles (p-value: 0.04). A poor-prognosis signature by the 70-gene assay was observed in 76% of BCs. Conclusions: BC with HER2+ gene profile is the most likely to respond with pCR (RCB 0) to trastuzumab-containing NCT. RCB scores as a function of NCT, molecular subtypes, and poor vs. good risk profile in the entire pt population will be presented.

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