Abstract P5-08-26: CYP1A2– A novel genetic marker for aromatase inhibitor response in the treatment of breast cancer patients

Abstract

Abstract Background: Endocrine resistance is a major obstacle for optimal endocrine treatment in breast cancer (BC). Several genetic markers for tamoxifen response have been proposed. Although some genetic markers have been proposed for response to aromatase inhibitors (AI), data is insufficient. The aim of this study was 1) to perform an exploratory analysis of genes involved in Absorption, Distribution, Metabolism, and Elimination (ADME) to find new predictive markers in a subset of the cohort and 2) examine these potential markers in relation to risk for events in the extended cohort. Materials and methods: In Lund, Sweden, 190 AI-treated primary breast cancer patients with estrogen receptor positive tumors, who underwent breast cancer surgery between 2002 and 2008, were followed until December 31st 2012. Clinical data were obtained from medical records and population registries. The impact of single nucleotide polymorphisms (SNPs) on risk for breast cancer events was conducted on a subset of the cohort followed until December 31st 2011 (13 cases, 11 controls) and analyzed with data from a DMET (TM) chip including 1931 SNPs in 225 ADME-related genes. Secondly, four SNPs in CYP19A1 and the significant SNPs from the first analysis were reanalyzed concerning disease-free survival in the extended cohort of 190 patients. Results: A CYP1A2 SNP was significantly associated with risk for early events among the 24 AI-treated BC patients both in the subset of the cohort, (P=0.0007) and in the extended cohort, adjusted HR 3.83 (95% CI 1.40-10.42). SNPs in CYP19A1 alone were not significantly associated with disease-free survival in any of the analyses. The impact of the CYP1A2 SNP was modified by a SNP in CYP19A1, where patients with both SNPs had increased risk for early events, adjusted HR 5.21 (95% CI 2.05-13.23) compared to other patients. Conclusion: This study identified a potential and new predictive marker in BC patients: CYP1A2 alone and CYP1A2 in combination with CYP19A1. If confirmed, these results may provide a way to more personalized medicine. Citation Format: Simonsson M, Veerla S, Markkula A, Rose C, Ingvar C, Jernström H. CYP1A2– A novel genetic marker for aromatase inhibitor response in the treatment of breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-26.