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.
Highlights
In 2010, it is estimated that more than 200,000 women will be newly diagnosed with invasive breast cancer in the United States [1], making it the most commonly diagnosed cancer in women
Bone mineral density as a marker of aromatase inhibitor (AI)-induced bone fragility In a substudy of the ATAC trial, there was a significant reduction in lumbar spine and hip bone mineral density (BMD; 2.2% and 1.3%, respectively) in patients receiving anastrozole over the first year of treatment; while BMD significantly increased in women treated with tamoxifen over the same time period (1.0% and 0.5% increase in lumbar spine and hip, respectively) [26]
AIs are widely used in the treatment of early-stage breast cancer
Summary
In 2010, it is estimated that more than 200,000 women will be newly diagnosed with invasive breast cancer in the United States [1], making it the most commonly diagnosed cancer in women. In a small cohort of the ELPh study, evaluation of concentrations of circulating inflammatory markers in patients with AI-induced arthralgia showed no significant change in the tested markers relative to pre-treatment concentrations or compared to women who did not report symptoms [94]. Interval since menopause was the only significant risk factor (possibly linked to cytokine activity or to a more precipitous drop in estrogen levels), with women who had their last menstrual period within 5 years of starting therapy more likely to develop joint symptoms compared to those whose last menstrual period was 10 years prior to starting therapy (73% versus 35%, adjusted odds radio, 3.39; 95% confidence interval, 1.21 to 9.44; P = 0.02) [62]. Alternatives include a drug holiday and/or switching to tamoxifen if clinically appropriate
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