• A five-year probability of breast cancer exceeding 1.7%, based on a validated risk assessment model (eg, the Gail model, BRCAPRO)
• Presence of the BRCA1 or BRCA2 mutation.
Tamoxifen is a selective estrogen receptor modulator (SERM) that blocks the effects of estrogen on breast tissue.43 Often referred to as an “antiestrogen,” it is approved for use in both premenopausal and postmenopausal women. In the Breast Cancer Prevention Trial,44 women at high risk for breast cancer who took tamoxifen for five years had about a 50% risk reduction for invasive breast cancer and a 30% risk reduction in noninvasive breast cancer. The usual dose of tamoxifen is 20 mg/d.
Adverse effects associated with tamoxifen use, however, include blood clots, stroke, and uterine cancer. Women should not take tamoxifen if they have a history of cataracts, are current hormone therapy users, are planning a pregnancy or have the potential for becoming pregnant, or have a history of stroke, deep venous thrombosis, or pulmonary embolus. Less serious adverse effects include menopausal symptoms, menstrual irregularities, headache, fatigue, nausea, and skin irritation.43
Raloxifene, though more commonly prescribed to prevent and treat osteoporosis, has been shown to reduce the risk for invasive breast cancer by 56% to 72%, compared with placebo45,46; it exerts estrogenic effects on bone and antiestrogenic effects on breast and endometrial tissue.47 This SERM is approved for breast cancer risk reduction only in postmenopausal women.48 Recommended use is 60 mg/d for five years.
Although raloxifene provides a risk reduction benefit comparable to that of tamoxifen against invasive breast cancer (ie, incidence rates of 4.4 and 4.3, respectively, per 1,000 women per year49), it does not appear to reduce the risk for noninvasive breast cancer (ie, ductal carcinoma in situ).50 Potential major complications attributed to raloxifene use include blood clots, stroke, and uterine cancer, although the risk for uterine cancer is lower than with tamoxifen use.49 Minor adverse effects include leg cramps, menopausal symptoms, edema of the extremities, and flulike symptoms. Contraindications are comparable to those associated with tamoxifen.48
Screening Recommendations Combined with mammography and breast ultrasound, the use of MRI to screen high-risk women is now being recommended, according to guidelines published in March 2007 by the American Cancer Society.20 Patient factors suggesting greatest benefit from annual MRI screening (combined with mammography) are listed in Table 3.4,20,51-55
In addition to patient-driven reduction strategies and the provider-initiated interventions for surveillance and management, monthly breast self-examination is encouraged, as are clinical breast examinations every six months.
Even with the most aggressive risk reduction program, not all breast cancers can be prevented. A key objective of high-risk screening and management is to identify patients with breast cancer at the earliest possible stage so that a cure is more likely to be achieved.
Conclusion Identifying and screening women at high risk for breast cancer are essential skills for all primary care providers. Maintaining a comprehensive list of referral sources for high-risk management and genetic counseling services in your area will allow you to partner with other professionals to provide patients with the best possible care. Women feel empowered by education, particularly the newly acquired knowledge about breast cancer risk reduction—and reassured, knowing that their providers are interested and well informed in this complex area of women’s health.
