AIs: implications for fractures in perimenopausal women with breast cancer

Abstract

Aromatase inhibitors (AIs) prevent the conversion of adrenal androgens into estrogens by the enzyme aromatase and thus impede the majority of estrogen production in peri- and postmenopausal women. By lowering estrogen levels, AIs inhibit tumor progression. Unlike other hormonal therapies, AIs produce no clinically relevant suppression of cortisol or aldosterone. Additionally, several large randomized trials comparing AIs with tamoxifen as first-line treatment of metastatic breast cancer have demonstrated similar or slightly superior clinical efficacy. Because of these attributes, AIs have become a widely popular breast cancer treatment in postmenopausal women. Recent instances of increased fracture risk have been reported among perimenopausal women using AI treatment. The use of AIs in perimenopausal women can decrease estrogen levels by approximately 90%, leading to the onset of premature menopause, increased bone turnover, and accelerated bone loss.1 The effects of AI-induced estrogen loss are less severe among pre- and postmenopausal women. Because estrogen is vital for maintaining bone health, perimenopausal women with breast cancer, like their menopausal counterparts, have demonstrated an increased risk of fractures while using AIs. In this article, investigators affiliated with RADAR (Research on Adverse Drug events And Reports), an established pharmacovigilance program, reviewed clinical trial reports and one observational study to determine the frequency and clinical characteristics of AI-associated fractures in menopausal women with breast cancer.