Tipping the Balance for the Primary Prevention of Breast Cancer

There are millions of postmenopausal women in the United States who are at risk for both osteoporosis and breast cancer, and both diseases cause thousands of deaths each year (1). Clearly, a preventive strategy is more attractive than treating progressive or advanced disease, but neither the primary care community nor medical oncologists have embraced chemoprevention of breast cancer as their own responsibility, despite the fact that professional organizations have endorsed primary prevention as a standard of care (2,3). In this issue of the Journal, LaCroix et al. (4) describe the effect of lasofoxifene in reducing the incidence of breast cancer in postmenopausal women with osteoporosis. Lasofoxifene appears to represent an advance in the progression of pharmacological agents at our disposal, which can reduce both the risk of fractures in women with osteoporosis and the risk of breast cancer in postmenopausal women (5–7), possibly because it binds with high affinity to both estrogen receptors (ER)-a and ER-b. A previously reported 42% reduction in the risk of vertebral fractures (13.5 vs 23.0 per 1000 person-years) at 3 years attributable to lasofoxifene is similar to that observed with raloxifene, estrogen therapy, oral bisphosphonates, and tibolone (8). The decreased risk of nonvertebral fractures is also similar to that reported in association with other antiresorptive therapies in women with osteoporosis. In contrast to lasofoxifene, however, raloxifene—the selective estrogen receptor modulator (SERM) currently approved by the US Food and Drug Administration for treatment of osteoporosis—does not reduce the risk of nonvertebral fractures, perhaps because lasofoxifene decreases markers of bone turnover and improves spine bone mineral density more than does raloxifene at a dose of 60 mg, although the two agents have similar effects on total hip bone mineral density (8,9). In order for a preventive strategy to be both effective and effi cient, we need an easily identified target population, criteria for identifying those who would benefit from a risk reduction strategy, a safe and effective agent, an informed group of practitioners who can provide care to the high-risk group, and an educated population of patients who understand the advantages and the risks of taking a drug to modify their risk. Multiple studies have shown that tamoxifen reduces the risk in women at increased risk of breast cancer (10,11). In addition, we now have several strategies to identify women at increased risk: quantitative risk models (12–14), increased mammographic density (15–17), circulating estrogen levels (18–20), and the presence of high-risk benign breast disease such as atypical hyperplasia and lobular carcinoma in situ (21,22). We now also have several agents that have been studied prospectively in randomized controlled trials that have examined benefits, life-threatening side effects, and quality-of-life outcomes. We have estimates of the population benefit of using SERMs for breast cancer risk reduction (1), and we have estimates of the cost per year of life saved (23,24). Yet, despite the fact that the number of women needed to treat to prevent a case of breast cancer is acceptable with both of the SERMs, tamoxifen and raloxifene, neither drug has been able to tip the clinical utility scale to broad usage within the high-risk population for