Exemestane for primary prevention of breast cancer in postmenopausal women

Abstract

The benefits and risks of exemestane for the primary prevention of breast cancer are discussed and compared with other breast cancer chemoprevention therapies. Selective estrogen-receptor modulators (SERMs) are the current mainstay for primary prevention of breast cancer. As an alternative, exemestane, an aromatase inhibitor, has been evaluated for breast cancer prevention in postmenopausal women. A study of 4560 high-risk postmenopausal women taking exemestane 25 mg daily for a median of three years found a 65% relative reduction in the annual occurrence of invasive breast cancer compared with placebo (0.19% versus 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18-0.70; p = 0.002) and a 53% reduction in invasive plus noninvasive breast cancer (0.35% versus 0.77%; hazard ratio, 0.47; 95% CI, 0.27-0.79; p = 0.04). Adverse effects from exemestane are generally mild, with the most common being diarrhea, joint pain, and menopausal-related symptoms. Importantly, exemestane did not increase the risks of endometrial cancers, thromboembolism, cardiovascular events, or cataracts. However, joint stiffness and arthralgia were more common when compared with tamoxifen or raloxifene. Ongoing clinical trials with other aromatase inhibitors are underway to evaluate the benefits and long-term skeletal risks. Exemestane 25 mg daily taken for at least three years is a new option for the prevention of breast cancer in high-risk postmenopausal women. Indirectly compared with SERMs, exemestane has a similar frequency of bothersome adverse effects without the risk of thromboembolic events or endometrial cancer, though an increased risk of osteoporosis is of concern.