Musculoskeletal symptoms in women on aromatase inhibitors for adjuvant breast cancer therapy

Background: Musculoskeletal symptoms are a major adverse effect associated with aromatase inhibitors (AIs), commonly used as adjuvant therapy for breast cancer in postmenopausal women. A detailed assessment of the natural history of these AI-associated musculoskeletal symptoms over the course of therapy (at least 5 years) has not been well documented. The impact of the musculoskeletal symptoms on persistence with treatment and health-related quality of life (HR-QOL) was also examined.;Methods: This was a follow up study of 205 women (68 breast cancer patients exposed to AIs, 137 unexposed women) previously enrolled in a 6-month study to characterize musculoskeletal pain among women on AI compared to women without a history of breast cancer at Mercy Medical Center, Baltimore MD. This study extended the follow-up of the women; all study participants were contacted an average of 3.5 years since study initiation. Musculoskeletal pain was reassessed using a 10cm visual analog scale (VAS) and persistence with treatment was evaluated using a self- administered questionnaire and verified with medical records. Linear regression models were used to examine the association between musculoskeletal pain and health- related quality of life (HR-QOL) assessed by the Medical Outcomes Study Short Form (SF-36) health survey.;Results: Among the women with breast cancer, a substantial proportion, 23.5% of the women who initiated Al therapy had discontinued treatment at the time of follow up primarily because of AI- associated musculoskeletal symptoms. Of those who persisted with AI therapy, after the initial increase within the first 6 months of AI use, the severity of symptoms remained stable. In the comparison group of postmenopausal women without a history of breast cancer, there were modest increases in musculoskeletal pain over the study period. The study also found musculoskeletal symptoms was negatively associated with health- related quality of life. Among women with breast cancer, those with musculoskeletal symptoms had statistically significantly lower HR-QOL scores in all sub-scales including the physical and mental component summary compared to those without musculoskeletal symptoms. In the comparison group, musculoskeletal pain was associated with lower scores in the physical component but there were no statistically significant differences in scores on the mental component between those with and without musculoskeletal symptoms.;Conclusion: Despite the known benefits of adjuvant hormonal therapy, many women discontinue treatment early because of AI- associated musculoskeletal symptoms and most fail to resume any type of hormonal treatment. The study findings also suggest among the women who persisted with treatment beyond 6 months, severity of musculoskeletal symptoms remained relatively constant 2.4 to 4.8 years after initiation of AI therapy. Furthermore, AI- associated musculoskeletal symptoms adversely affects both the physical and mental health of women with breast cancer, in contrast to the comparison group, where the impact of musculoskeletal pain was only on the physical domain of HR-QOL. Musculoskeletal symptoms needs to be addressed and managed by clinicians focusing on its impact on mental health to improve health- related quality of life and persistence with treatment for better treatment outcomes.