Polymorphisms of the aromatase gene (CYP19A1) and benefit of aromatase inhibitors (AIs) in metastatic breast cancer (mBC) patients.

608 Background: Germline genotypic polymorphisms in CYP19A1 have been associated with differential benefit from treatment with AIs in patients with mBC, but validation is lacking. Methods: We retrospectively identified patients with ER-positive mBC treated with a 3rd generation AI. DNA was obtained from archival paraffin-embedded tumors and genotyped for 74 polymorphisms in 20 candidate genes, including CYP19A1 using the Sequenom MassARRAY Platform. The CYP19A1 Arg264Cys (rs700519) variant was analyzed by Pyrosequencing. The CYP19A1 (TTTA)n(rs60271534) and TCT Ins/Del (rs11575899) variants were genotyped by fragment analysis.Primary endpoint was time to treatment failure (TTF), analyses being undertaken using Cox’s regression to estimate the hazard ratio for risk of failure per allele. Results: 308 patients were included. Mean TTF was 15 months (range 1 to 58). Two sets of analyses were undertaken. The first were confirmatory analyses for the CYP19A1 variants rs4646, rs10459592 and rs4775936, previously a...