Gene signatures as predictors of response to neoadjuvant chemotherapy (NCT) with docetaxel, doxorubicin, cyclophosphamide (TAC), or AC and nab-paclitaxel (nab-P) and carboplatin ± trastuzumab in patients (pts) with stage II-III and inflammatory breast cancer (IBC).

Abstract

540 Background: 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 × 4, followed by 3 weekly doses of carboplatin (carbo) at an AUC 2,and nab- P 100 mg/m2, repeated as 28 day cycles × 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. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agendia Abraxis BioScience Agendia Abraxis BioScience