Triple-negative breast cancer subtypes and pathologic complete-response rate to neoadjuvant chemotherapy: Results from the GEICAM/2006-2003 study.

Abstract

1024 Background: Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy (CHT) and targeted agents. In a recent study, Lehmann et al. (JCI 2011) identified six molecular subtypes of TNBC, characterized on the basis of gene ontologies and differential gene expression. However, their clinical utility remains unclear. We aimed to explore the clinical relevance of these molecular subtypes in TNBC determining differences in response to neoadjuvant chemotherapy in a randomized phase II trial, the GEICAM/ 2006-03. Methods: The GEICAM/ 2006-03 study evaluated a regimen of anthracyclines and taxanes +/- carboplatin in the neoadjuvant treatment of patients (pts) with TNBC (Alba, BCRT 2012). We determined TNBC molecular subtypes in FFPE pre-treatment tumor biopsies from pts recruited in this study. Gene expression profile was determined using HTA 2.0 arrays (Illumina). Subtypes were identified with the online tool TNBC type (http://cbc.mc.vanderbilt.edu/tnbc). Finally, we explored the association of the Lehmann subtypes with the pathological complete response (pCR) in breast and axilla (Miller and Payne criteria) using Fisher's exact test. Results: From the 94 enrolled pts, we processed 46 pre-treatment tumor samples in a central lab and isolated high-quality RNA for microarray analysis in 39 (42%); 7 samples are still pending to be analyzed. Tumors were classified as follows: 4 BL1, 2 BL2, 8 IM, 5 LAR, 3 M, 3 ML with 7 pts that couldn't be assigned to any subtype and were not included in this analysis. Three (75%) of the BL1 subtype pts achieved a pCR (p-value=0.075). In contrast, IM and LAR achieved the lowest pCR rates (12% and 20%, respectively). In the carboplatin-treated patients, 100% of BL1 patients showed pCR (p-value=0.033) in contrast with none of the IM and LAR pts. Conclusions: Our preliminary findings suggest that TNBC subtypes can predict tumor response to neoadjuvant CHT, supporting their potential clinical utility in diagnosis, treatment selection and drug development, bringing TNBC pts a step closer to personalized medicine.