ArticleBreast cancer research and treatment2026
ESR1 polymorphisms were associated with aromatase inhibitors induced musculoskeletal symptoms in breast cancer patients.
Article in Breast cancer research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeAromatase Inhibitors Associated Musculoskeletal Symptoms (AIMSS) are common side effects among hormone receptor-positive breast cancer patients, significantly affecting patients' treatment adherence and quality of life. The individual genetic susceptibility mechanism underlying AIMSS was not well understood yet. This study aimed to validate the association between genetic polymorphisms and AIMSS among Chinese breast cancer patients.
methodsThis was a cross-sectional study. Participants were recruited from a tertiary hospital in China from May 2023 to June 2024. Musculoskeletal symptoms were measured using the Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) among hormone receptor-positive patients receiving aromatase inhibitor therapy. Six genes (i.e., ESR1, ESR2, RANK, OPG, TCL1A and CYP19A1) related 20 SNPs were tested. Multivariate linear regression analysis was used to explore the association between different genotypes and the severity of AIMSS.
resultsAmong 171 participants, the standardized M-SACRAH score was 3.33 (IQR 0.00-9.17) and the standardized WOMAC score was 5.83 (IQR 2.08-17.29). Patients carrying the ESR1 rs9340799 AG genotype (vs. AA) had a significant reduction in the severity of hand joint symptoms [adjusted β = -4.51, 95% CI: -8.29, -0.73, p = 0.020] and knee/hip joint symptoms [adjusted β = -4.44, 95% CI: -8.49, -0.39, p = 0.032]. The ESR1 rs2077647 TC genotype (vs. TT) was related to lower level of hand joint symptoms [adjusted β = -5.03, 95% CI: -8.69, -1.37, p = 0.007] and knee/hip joint symptoms [adjusted β = -5.04, 95% CI: -8.97, -1.12, p = 0.012]. The ESR1 rs2234693 TC genotype (vs. TT) [adjusted β = -4.06, 95% CI: -8.09, -0.03, p = 0.049] was associated with lower level of knee/hip joint symptoms. No significant associations emerged between ESR2, RANKL, OPG, TCL1A, or CYP19A1 variants and AIMSS.
conclusionsThis study preliminarily validated the association between ESR1 polymorphisms (rs9340799, rs2077647, and rs2234693) and aromatase inhibitor associated musculoskeletal symptoms in hormone receptor-positive breast cancer among Chinese patients. Future research should focus on dissecting their molecular mechanisms, and integrating genetic data with clinical interventions to optimize the management strategies of musculoskeletal toxicity.
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