Abstract P1-03-05: Genetic variant in the OPG gene is associated with aromatase inhibitor-related musculoskeletal toxicity in breast cancer patients

Abstract

Abstract Background Aromatase inhibitor (AI) therapy is associated with musculoskeletal toxicity, which adversely affects quality of life and therapy adherence. Our objective was to evaluate genetic predictors for endocrine therapy-related musculoskeletal pain in a prospective cohort study, which was previously published. Patients & methods 254 early breast cancer patients starting AI (n=159) or tamoxifen therapy (n=95) were included in this genetic biomarker study. Musculoskeletal symptoms were assessed at baseline and at 3, 6 and 12 months thereafter. AI-induced musculoskeletal pain was defined as an increase in arthralgia or myalgia relative to baseline. Single nucleotide polymorphisms (SNP) in candidate genes involved in estrogen signaling or reported to have associations with AI-related musculoskeletal pain or estrogen levels were selected. Of the 40 selected SNPs, 7 failed genotyping and were excluded from further analysis. Results Twenty SNPs exhibited a minor allele frequency <0.05 and were omitted from the final analysis. Overall, 13 SNPs in CYP19, CYP17, osteoprotegerin (OPG) and estrogen receptor 1 were included. 74% of AI-users reported new or worsened musculoskeletal pain compared to 33% of tamoxifen-treated patients. The OPG SNP rs2073618 was significantly associated with AI-induced musculoskeletal toxicity after correction for multiple testing (p=0.039). None of the other SNPs showed significant associations, both in AI and tamoxifen-treated patients. Conclusion The SNP rs2073618 in OPG predicts the risk of musculoskeletal symptoms with AI therapy, which has not been reported so far. Validation of this finding and further functional studies are needed. Citation Format: Anneleen Lintermans, Kathleen Van Asten, Annouschka Laenen, Thomas Van Brussel, Johan Verhaeghe, Dirk Vanderschueren, Diether Lambrechts, Patrick Neven. Genetic variant in the OPG gene is associated with aromatase inhibitor-related musculoskeletal toxicity in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-03-05.