Abstract LB-194: AhR Arg554Lys impacts tumor ER expression and endocrine treatment response in breast cancer

Abstract

Abstract Introduction: Markers for treatment resistance in breast cancer are needed. The Aryl hydrocarbon receptor (AhR) is involved in the regulation of estrogen metabolism. Previous studies have observed a crosstalk between AhR and the estrogen receptor (ER), indicating that the AhR may be of importance in the response of endocrine treatment. Materials and methods: A functional polymorphism in the AhR Arg554Lys (G>A) was analyzed in a cohort of 634 breast cancer patients included at their preoperative visits in Lund, Sweden between 2002 and 2008. AhR genotypes were studied in relation to ER status and risk for breast cancer events. Results: The frequencies of the AhR GG/ GA/ AA genotypes were 82.0%, 16.7%, and 1.3%, respectively. There was a trend towards increasing frequency of ER+ tumors with increasing number of A-alleles (P-trend = 0.03). Since few patients had the A/A genotype, patients with the G/A and A/A genotypes were combined in the survival analyses of the 576 patients with invasive tumors, no preoperative treatment, and no events detected on the postoperative metastases screen. Overall, AhR was not associated with event-free survival (LogRank P = 0.22). Among patients ever treated with chemotherapy or radiotherapy, AhR was not associated with event-free survival (LogRank P = 0.24 and P = 0.18, respectively). However, among tamoxifen-treated patients with ER+ tumors, AhR G/G carriers had a significantly lower risk for breast cancer events (LogRank P = 0.005), adjusted HR 0.53 (95% CI 0.29-0.94). This association was confined to patients who had received both tamoxifen and aromatase inhibitor (AI) switch treatment (LogRank P = 0.0002), adjusted HR 0.23 (0.09-055), while no association was seen in patients treated with tamoxifen only (LogRank P = 0.56). AI-treated patients with the G/G genotype had an even lower risk for breast cancer events than tamoxifen-treated patients (LogRank P = 0.005), adjusted HR 0.39 (0.19-0.81). Again this was only seen in patients who had received both AI and tamoxifen, but not in patients who had received AI but no tamoxifen treatment. Adjustments were made for age at inclusion, axillary lymph node involvement, invasive tumor size, and histological grade. Further adjustment for smoking status did not materially change the results. Conclusion: The functional AhR Arg554Lys polymorphism may impact tumor ER expression and response to endocrine switch treatment with both AI and tamoxifen in breast cancer patients. Citation Format: Maria Simonsson, Andrea Markkula, Carsten Rose, Christian Ingvar, Helena C. Jernström. AhR Arg554Lys impacts tumor ER expression and endocrine treatment response in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-194.