Purpose: Neoadjuvant chemotherapy (NCT) using anthracyclines and taxanes is a standard treatment for locally advanced breast cancer. Efficacy of NCT is however variable among patients and predictive markers are expected to guide the selection of patients who will benefit from NCT. A promising approach stand with polymorphisms located in genes encoding drug transporters, drug metabolizing enzymes and target genes which can affect drug efficacy. Our study investigated the potential of 37 polymorphisms to predict response to NCT in breast cancer.
Methods: 118 women with breast adenocarcinoma were treated with FEC100 and taxotere. Genotyping was performed on germline DNA using the BioMark platform (Fluidigm). Pathological complete response (pCR) according to Sataloff criteria was correlated to clinical characteristics and genotypes using univariate and multivariate analyses.
Results: 25 patients (21.2%) reached complete pathologic response. pCR rate is increased in SBRIII (p = 0.009), ER negative (p = 0.005) and triple negative (p = 0.006) tumors. pCR rate is significantly increased for patients carrying at least one variant allele for BRCA1, ERCC1 or SLCO1B3, and for patients homozygous for CYP1B1. The combination of ERCC1 and CYP1B1 polymorphisms is a potential predictor of NCT response in breast cancer (pCR rate reached 50 vs 21.2% for unselected patients), and particularly in ER + breast cancer subtype where pCR rate reached 41.2 vs 13.5% for unselected patients.
Conclusions: This study is the first to report ERCC1, BRCA1 and SLCO1B3 as markers of response to NCT in breast cancer. ERCC1/CYP1B1 combination might be of particular interest to predict response to NCT in breast cancer and particularly to help NCT indication for ER+ breast tumors.
Keywords: Breast cancer; CYP1B1; ERCC1; Neoadjuvant chemotherapy; Predictive factor; Single nucleotide polymorphism.