Adjuvant aromatase inhibitors in breast cancer therapy: significance of musculoskeletal complications

Aromatase inhibitors, which offers profound suppression of estrogen synthesise, have been introduced as long-term adjuvant therapeutic agents for postmenopausal women with breast cancer. Compared with tamoxifen treatment, which has long been the standard of care in anti-estrogen therapy, third-generation aromatase offer superior efficacy with regard to disease-free survival rates. The aromatase inhibitors anastrozole, letrozole and exemestane have a different toxicity profile from tamoxifen and are relatively free of some of the side effects associated with tamoxifen, such as deep vein thrombosis and uterine malignancies. They can, however, cause bone and joint pain (arthralgia), as well as the loss of bone mineral density and an increased incidence of fractures. These events appear to arise as class effects for the aromatase inhibitors, as they occur with all members of this structurally and mechanistically diverse group of drugs. Here we summarize the latest data on the efficacy of aromatase inhibitors and their effects on the risk of arthralgia and other musculoskeletal complications; notably from five ongoing clinical trials comparing aromatase inhibitors with tamoxifen or placebo.