Abstract PS4-12: Potential value of FOXA1 expression as genomic predictor of response to docetaxel and carboplatin neoadjuvant (NA) chemotherapy in patients with triple negative breast cancer (TNBC)

Background: TNBC is a particularly aggressive subtype with high recurrence rates and poor long-term survival. Anthracycline-free regimens based on docetaxel plus carboplatin (TCb) achieve around 50-55% pathologic complete responses (pCR) which correlates with better survival outcomes. Identification of genomic predictors of response is key to individualize therapies for this heterogeneous breast cancer (BC) subgroup. FOXA1 is a pioneer factor for androgen (AR) and estrogen receptors (ER). Its under-expression has been linked to cancer stemness in TNBC and better prognosis in ER-positive BC. The differential expression of AR, FOXA1 and BRCA1 is associated with sensitivity to chemotherapy in TNBC patients. Data support the plasticity role of FOXA1 driving basal to luminal BC cells by inducing luminal genes but also by repressing the basal phenotype and thus, tumor aggressiveness, although its role as a biomarker in TNBC is still controversial. We have analyzed RNAseq data of FOXA1 and AR in a series of TNBC tumors homogenously treated with neoadjuvant TCb to study their correlation with survival and response. Methodology: 300 TNBC patients have been included in a multicenter, prospective, non-randomized trial aimed to identify predictors of response to TCb in the neoadjuvant setting (NCT01560663). 278/300 patients were evaluable. PAM50 subtypes (NanoString nCounter) and RNAseq (HiSeq2500) were analyzed for those patients with both available samples and evaluable pathological response (n=208). Correlations were studied by the Kendall method. Linear or logistic regressions were adjusted for univariant analysis depending on numerical or categorical response variables, respectively. Results: FOXA1 and AR were differentially expressed between basal and non-basal tumor subtypes (PAM50), being overexpressed in non-basal (p Citation Format: Sara Lopez-Tarruella, Maria del Monte-Millan, Enrique Alvarez, Yolanda Jerez, Jose Angel Garcia Saenz, Isabel Echavarria, Fernando Moreno, Ivan Marquez-Rodas, Coralia Bueno-Muino, Blanca Herrero, Maria Cebollero, Rocio Ramos-Medina, Nerea Lobato, Ricardo Gonzalez del Val, Maria Isabel Palomero, Santiago Lizarraga, Uriel Bohn, Ana Isabel Ballesteros, Patricia Rincon, Tatiana Massarrah, Inmaculada Ocana, Lucia Villarejo, Charles M Perou, Miguel Martin. Potential value of FOXA1 expression as genomic predictor of response to docetaxel and carboplatin neoadjuvant (NA) chemotherapy in patients with triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-12.