Aromatase Inhibitors in Breast Cancer Prevention

Objective: To review the literature evaluating the benefit and tolerability of aromatase inhibitors (AIs) in breast cancer risk reduction. Data Source: A PubMed search (1966-July 2014) was conducted using the key terms breast cancer risk reduction, with anastrozole, exemestane, or letrozole, or aromatase inhibitors. Abstracts from recent breast cancer symposia were reviewed. Study Selection and Data Extraction: All English-language articles were reviewed for inclusion. The references of articles were reviewed for additional studies. The review focused on AI trials in women without preexisting cancer; review articles, preclinical studies, and studies of AI use in early-stage cancer were excluded. Data Synthesis: Lifestyle modifications, surgery, and selective estrogen receptor modulators (SERMs) are options for women at high risk for breast cancer compared with the general population. Statements published by various organizations help guide appropriate patient selection. Toxicities with SERMs, including increased risk for endometrial cancer, thromboembolic events, and cataracts, have limited their utility. AIs inhibit the endogenous production of estrogen and are mechanistically distinct from SERMs. Placebo-controlled trials with exemestane and anastrozole in postmenopausal women with breast cancer risk factors demonstrated at least 50% efficacy in invasive breast cancer reduction and were well tolerated. Vasomotor symptoms were experienced, but no differences in fractures or cardiovascular events were observed. Summary: Exemestane and anastrozole appear to offer benefit for postmenopausal woman at high risk for invasive breast cancer and are well tolerated. AIs offer an alternative for high-risk postmenopausal women desiring chemoprevention but with SERM contraindications. More trials are warranted to help further guide appropriate patient selection.