Basal-, Luminal-, and HER2- Molecular Subtype, and the MammaPrint 70-Gene Signature as Predictors of Response to Neoadjuvant Chemotherapy (NCT) with Docetaxel, Doxorubicin, Cyclophosphamide (TAC), or AC and <i>Nab</i>-Paclitaxel and Carboplatin +/- Trastuzumab in Patients (Pts) with Stage II-III and Inflammatory Breast Cancer (BC).
Authors: G. Somlo, S. Lau, P. Frankel, C. Garberoglio, L. Kruper, Y. Yen, T. Luu, A. Hurria, C. Chung, J. Mortimer, J. Yim, I. Paz, O. Krijgsman, L. Delahaye, L. Stork-Sloots, R. Bender
Journal: Cancer Research (2009)

Abstract Background: Pathologic complete response (pCR) and minimal residual cancer burden (RCB scores of 0 [pCR]-1[near CR]) after NCT may predict for improved survival (Symmans et al. J Clin Oncol 25:4414-22, 2007). Hence, improved NCT regimens in conjunction with molecular markers that predict for both response and/or resistance are needed. Materials and Methods: 115 pts with stages II-III BC were to be prospectively randomized to receive 6 cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 with filgrastim support (TAC, arm A) versus a novel regimen of A 60 mg/m2 and C 600 mg/m2 given every 2 weeks x 4, followed by 3 weekly doses of carboplatin (AUC 2) and nab-paclitaxel 100 mg/m2 repeated as 28 day cycles x 3 (arm B). Pts with HER2 + BC received NCT similar to arm B, but with the addition of 12 weekly doses of trastuzumab given together with carboplatin and nab-paclitaxel (arm C). Core biopsies were performed prior to NCT and were preserved fresh frozen. 70-gene (MammaPrint™) profiling and 80-gene profiling (van de Vijver et al. NEJM 347:1999-2009, 2002) to categorize all tumors for basal-, HER2-, and luminal subtypes were carried out. We set out to assess the predictive value of Mammaprint scores (poor vs. good), as well as basal, vs. luminal, vs. HER2 molecular subtype profiling, for response to treatment on arms A vs. B vs. C. Responses were dichotomized as complete or near complete response (Symmans RCB scores of 0-1) vs. suboptimal response (RCB score &amp;gt; 1). Results: Sufficient amount of BC tissue and good quality RNA for gene array assessment were procured in 64% of the first 90 patients who have undergone pre-treatment core biopsies, and then proceeded to NCT, followed by definitive surgery. Here we report on the first 50 pts with complete set of data analyzed. The median age was 50 years (range:31-69). Pts were treated for stage II (49%) and III locally advanced (41%), and inflammatory BC (10%). By gene profiling, 28% of the tumors were HER2-type (vs. 38% by IHC 3+, or FISH, representing all pts treated on arm C), 26% basal-type, 42% luminal-type, and 4% borderline luminal-type. Poor-prognosis signature by the 70-gene (MammaPrint) assay was observed in 74% of pts: 92% of HER2-type, 100% of basal-type, and 52% of luminal-type tumors were characterized as poor-risk by the 70-gene assay. Following NCT, Symmans RCB scores of 0-1 were observed in 71% of pts with HER2-type, in 38% with basal-type, and 28% of pts with luminal-type molecular subtype characteristics. Conclusion: BC with HER2- and basal-molecular subtypes are more likely to respond to NCT and is frequently associated with poor-risk characteristics as determined by the 70-gene assay. The complete analysis of correlations among response to specific sets of NCT, molecular subtype, and 70-gene assay results in the entire pt population will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2026.