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Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management.

ABSTRACT: Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes.

SUBMITTER: Gaillard S

PROVIDER: S-EPMC3219175 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management.

Gaillard Stéphanie S Stearns Vered V

Breast cancer research : BCR 20110314 2

Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including os ...[more]

PMID: 21457526

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Project description:Treatment with aromatase inhibitors (AIs) is fundamental in women with hormone receptor-positive breast cancer in the adjuvant as well as the metastatic setting. Even though it is considered to be a well-tolerated therapy, aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) is the most common adverse event encountered by breast cancer patients. CDK4/6 inhibitors have emerged as a new treatment strategy in metastatic hormone receptor-positive breast cancer. However, the impact of CDK4/6 inhibitors on musculoskeletal symptoms caused by AIs is not well-defined. This systematic review aims to identify the frequency of joint symptoms induced by treatment with AIs and CDK4/6 inhibitors in the metastatic setting. Eligible articles were identified by a search of existing literature for the period 2005/01/01-2021/01/01; The algorithm consisted of a predefined combination of the following keywords "breast", "cancer", "aromatase inhibitors", "CDK4/6", "phase III". This study was performed in accordance with PRISMA guidelines. All randomized controlled Phase III trials (RCTs) evaluating the administration of third-generation aromatase inhibitors (AIs) and CDK4/6 inhibitors in postmenopausal women in the metastatic setting were considered eligible for this review. Overall, 16 randomized control trials (RCTs) were retrieved, of which nine studies explored the administration of AIs in the metastatic setting and seven studies investigated the combination of CDK4/6 inhibitors and AIs. Arthralgia was reported in 1-47% of patients treated with AIs and 5.8-33.3% of patients treated with CDK4/6 inhibitors. Myalgias occurred in 2-23.7% of patients receiving AIs compared with 4.8-11.9% of patients treated with CDK4/6 inhibitors. The incidence of back pain was 7-32.9% vs. 2.9-8.5% in postmenopausal women with metastatic disease treated with AIs and CDK4/6 inhibitors, respectively. Bone pain was reported in 7-32.9% of postmenopausal women treated with AIs and 2.9-8.5% of women treated with CDK4/6 inhibitors. AI treatment-induced musculoskeletal syndrome is an adverse event affecting over one-third (20-47%) of postmenopausal patients treated with AIs that often leads to treatment discontinuation. Data from RCTs provide evidence that the incidence of musculoskeletal symptoms is relatively decreased upon CDK4/6 inhibitor administration. CDK4/6 inhibitors may provide a protective role against AIMSS development.

Project description:Almost one-half of aromatase inhibitor (AI)-treated breast cancer patients experience AI-associated musculoskeletal symptoms (AIMSS); 20%-30% discontinue treatment because of severe symptoms. We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from previously conducted trials. We pooled patient-level data from 3 randomized trials testing interventions (omega-3 fatty acids, acupuncture, and duloxetine) for AIMSS that had similar eligibility criteria and the same patient-reported outcome measures. Only patients with a baseline Brief Pain Inventory average pain score of at least 4 of 10 were included. The primary outcome examined was 2-point reduction in average pain from baseline to week 12. Variable cut-point selection and logistic regression were used. Risk models were built by summing the number of factors statistically significantly associated with pain reduction. Analyses were stratified by study and adjusted for treatment arm. For the 583 analyzed patients, the 4 factors statistically significantly associated with pain reduction were Functional Assessment of Cancer Therapy Functional Well-Being greater than 24 and Physical Well-Being greater than 14 (higher scores reflect better function), and Western Ontario and McMaster Universities Osteoarthritis Index less than 50 and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands less than 33 (lower scores reflect less pain). Patients with all 4 factors were greater than 6 times more likely to experience at least a 2-point pain reduction (odds ratio = 6.37, 95% confidence interval = 2.31 to 17.53, 2-sided P < .001); similar results were found for secondary 30% and 50% pain reduction endpoints. Patients with AIMSS who have lower symptom and functional distress at study entry on AIMSS intervention trials are more likely to experience meaningful pain reduction. Baseline symptom and functional status should be considered as stratification factors in future interventional trials.

Dataset Information

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management.

Publications

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management.

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