Genetic variation in CYP19A1 and occurrence of adverse events in exemestane treatment with early breast cancer patients in the Dutch TEAM trial.

Abstract

e22152 Background: Aromatase inhibitors (AI) are an important part of treatment of endocrine sensitive breast cancer. Adverse events in patients treated with AI’s often cause treatment discontinuation. The most common adverse events, such as arthralgia, myalgia and hot flushes are probably caused by estrogen deprivation and predict treatment efficacy. It is unclear which patients are at risk to develop these adverse events. The aim of this study was to examine if SNP’s in the CYP19A1 gene can predict the occurrence of adverse events in breast cancer patients treated with adjuvant exemestane. Methods: Patients of whom tissue was available and were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. DNA was isolated from tumor samples and 30 SNPs were identified using a tagging SNP approach, aiming for 80% coverage of CYP19A1. Genotypes were determined with taqman assays. Primary endpoint of the study was the occurrence of adverse events. Secondary endpoints were the occurrence of hot flushes, arthralgia, and myalgia. Results: 807 patients were included in the analyses and genotypes were obtained in 722 cases. One SNP, rs8031311, was associated with a higher incidence of adverse events with an odds ratio of 2.8. Four SNP's were associated with an increased incidence of hot flushes: rs934635, rs4775928, rs16964189, rs6493496 with odds ratio’s of 2.9, 1.8, 1.8 and 2.6 respectively. No association was found between variation in CYP19A1 and the occurrence of arthralgia or myalgia. Conclusions: Germline variation in the CYP19A1 gene is related to the occurrence of adverse events, specifically hot flushes, in early breast cancer patients treated with exemestane. These findings may contribute to the individualization of hormonal therapy in breast cancer. [Table: see text]