Prognostic and predictive value of circulating ESR1 mutations in metastatic breast cancer patients (mBC) progressing under aromatase inhibitor (AI) treatment.

Abstract

511Background: We recently reported that the detection of somatic and circulating activating ESR1 mutations is related to AI resistance in hormone receptor positive (HR+) mBC (Sefrioui et al., 2015). We aimed to evaluate the predictive and prognostic values of circulating ESR1 mutations detection at time of progression in mBC patients under AI. Methods: This study is a monocentric retrospective analysis of all consecutive patients treated with first-line AI for HR+mBC from 2008/01 to 2010/12. ESR1 circulating mutations rates (D538G, Y537S/N/C) were assessed by droplet digital PCR on plasma samples at progression. The impact of the mutational status on OS, PFS and clinical response to subsequent treatments was determined by univariate and multivariate analysis. Results: A total of 144 HR+mBC patients was analyzed. Median follow-up from initiation of AI was 40 months (range 4-94). At progression, 44 patients (30.6 %) presented at least one ESR1 circulating mutation (D538G 54%, Y537S 45%, Y537N 34%, Y537C 4%...