Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients.

Autor: Borrie AE; Department of Medicine, Division of Clinical Pharmacology, Western University, London, ON, Canada.; Department of Physiology and Pharmacology, LHSC-University Hospital, Western University, Room B9-116, 339 Windermere Road, London, ON, N6A 5A5, Canada., Rose FA; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada., Choi YH; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada., Perera FE; Department of Oncology, Western University, London, ON, Canada., Read N; Department of Oncology, Western University, London, ON, Canada., Sexton T; Department of Oncology, Western University, London, ON, Canada., Lock M; Department of Oncology, Western University, London, ON, Canada., Vandenberg TA; Department of Oncology, Western University, London, ON, Canada., Hahn K; Department of Oncology, Western University, London, ON, Canada., Younus J; Department of Oncology, Western University, London, ON, Canada., Logan D; Department of Oncology, Western University, London, ON, Canada., Potvin K; Department of Oncology, Western University, London, ON, Canada., Yaremko B; Department of Oncology, Western University, London, ON, Canada., Yu E; Department of Oncology, Western University, London, ON, Canada., Lenehan J; Department of Oncology, Western University, London, ON, Canada., Welch S; Department of Oncology, Western University, London, ON, Canada., Teft WA; Department of Medicine, Division of Clinical Pharmacology, Western University, London, ON, Canada.; Department of Physiology and Pharmacology, LHSC-University Hospital, Western University, Room B9-116, 339 Windermere Road, London, ON, N6A 5A5, Canada., Kim RB; Department of Medicine, Division of Clinical Pharmacology, Western University, London, ON, Canada. richard.kim@lhsc.on.ca.; Department of Physiology and Pharmacology, LHSC-University Hospital, Western University, Room B9-116, 339 Windermere Road, London, ON, N6A 5A5, Canada. richard.kim@lhsc.on.ca.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2020 Sep; Vol. 183 (2), pp. 365-372. Date of Electronic Publication: 2020 Jul 06.
DOI: 10.1007/s10549-020-05777-1
Abstrakt: Purpose: Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer.
Methods: One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia.
Results: More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia.
Conclusions: Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.
Databáze: MEDLINE
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