Aromatase Inhibitors and Bone Health in Women With Breast Cancer

Abstract

The role of aromatase (estrogen synthetase) inhibitors (AIs) in breast cancer has expanded since their introduction in the mid-1990s. They are superior to tamoxifen in the treatment of postmenopausal women with estrogen-dependent tumors in the metastatic, neoadjuvant, and adjuvant settings. The profound estrogen depletion with AIs is responsible for improved antitumor effect but has led to concerns about healthy organs such as bone. This is particularly important in postmenopausal patients already at risk of osteoporosis and bone fracture because of premature menopause and toxic effects from chemotherapy and steroids. Compounding this, 80% of metastases develop in bone, which increase the risk of fracture through osteoclast-mediated destruction of surrounding bone. The American Society of Clinical Oncology (ASCO) currently recommends an AI as adjuvant therapy in postmenopausal women with hormone receptor–positive early breast cancer, either as initial monotherapy or after tamoxifen therapy. Trials examining their use beyond 5 years and their role as preventatives in healthy women are underway. Therefore, it is imperative that oncologists are familiar with long-term toxicities associated with AI therapy. This review summarizes emerging preclinical and clinical data related to the effects of AIs on bone mineral density, markers of bone turnover, and clinical fracture rates, and offers surveillance and clinical management recommendations with respect to bone health in women receiving chronic AI therapy.