IDENTIFICATION OF BIOMARKERS ASSOCIATED WITH COMPLETE PATHOLOGICAL RESPONSE IN THE NACATRINE TRIAL

Pathologic complete response (pCR) is an essential prognostic outcome for patients with triple negative breast cancer (TNBC). In this study, we performed a gene expression profile analysis to select candidate predictive biomarkers for pCR in TNBC patients who would receive neoadjuvant chemotherapy (NAC) and identify a profile of patients who could benefit from NAC. We evaluated the expression of genes in TNBC in untreated samples to associate with the outcome of NAC. The RNA was extracted from tissue biopsy and the gene expression was analyzed by nCounter® Breast Cancer^™ panel. The gene counts were normalized by housekeeping. For statistical significance, the T-test was used with p-value <0.05 and fold-change ≥ 2. For statistical analyses, SPSS software version 23 was used. Of the 66 patients included for the gene expression profile analysis, 24 had pCR and 42 had the residual disease at the primary endpoint. Twenty-four differentially expressed genes were identified when compared between pCR and residual disease, and 18 genes were underexpressed (HEMK1, FOXC2, ZBTB16, DLL4, SNAI1, TFF1, VEGFA, FGF1, ADCY9, BNIP3, INHBA, HAS1, C5orf38, RAD52, PGR, KCNB1, PLA2G4F, GRIN2A) and 6 overexpressed (ALDH1A1, CXADR, CXCL9, FGL2, HDAC2, MCM2) with p-value < 0.001. We performed a multivariate logistic regression model to predict pCR and showed a significant association between the HEMK1, KCNB1, VEGFA and MCM2 gene with pCR (OR= 0.048, 95% CI = 0.006 – 0.368; p = 0.004; OR= 0.061, 95% CI = 0.009 – 0.422; p = 0.05; OR = 0.028, 95% CI = 0.003 -0.241; p = 0.01; OR = 16.35, 95% CI = 2.326 – 15.01; p = 0.05) respectively. Genes are involved in important pathways such as estrogen receptor signaling (HEMK1), DNA damage repair (KCNB1 and MCM2), MAPK, PI3K, proliferation, cytokine, and chemokine signaling (VEGFA). Differential expression of HEMK1, KCNB1, VEGFA, and MCM2 genes was predictive of pCR in samples without any treatment with a significant OR, suggesting that these markers are validated and can be used to select patients for or not cytotoxic chemotherapy.