Significant research over the past three decades has focused on the screening, early detection, and treatment of breast cancer. More recently, efforts have focused on primary prevention, particularly in women who are deemed to be at increased risk for the disease. Surgical prevention with bilateral mastectomy was the traditional approach, but there were no conclusive studies supporting the benefits of prophylactic mastectomy. More recently, Hartmann et al. have demonstrated, using a retrospective study design, that prophylactic mastectomies reduce the risk of breast cancer by approximately 90%. A decision model suggests that prophylactic mastectomies could extend survival in young women with BRCA1 and BRCA2 mutations, but in older women prophylactic surgery will have little, if any, impact on survival. Given the morbidity associated with prophylactic surgery, this is generally not an approach that should be considered in an older patient population.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 trial, tamoxifen significantly decreased the risk of both invasive and noninvasive breast cancer by approximately 50% compared to placebo at 55-month median follow-up.

Eligibility for the trial was based on a breast cancer risk score calculated by the Gail Model, and, given the increased risk of breast cancer with age, all women over the age of 60 were eligible to participate. The reduction in risk was seen in all groups regardless of age at enrollment; 30% of the participants were over 60 years of age and 6% were over 70. Unfortunately, tamoxifen therapy was associated with significantly increased risks of thromboembolic disease and endometrial cancer. These risks are substantially higher in women over 50 than in women under the age of 50 and alter the therapeutic index of tamoxifen as a preventive agent in older women. In moderate-risk white women, the risks associated with tamoxifen are greater than the benefits after age 60, and in moderate-risk black women, the risks exceed the benefits by age 50. In general, the risk/benefit analysis of tamoxifen for the prevention of breast cancer weighs strongly against recommending that older women take tamoxifen for primary prevention unless they are at extraordinary risk of breast cancer in the next 5 years. Because the majority of breast cancer occurs in women over age 60, alternative chemoprevention strategies are desirable.

Other potential hormone-based strategies under consideration include newer selective estrogen receptor modulators (SERMs) and, for postmenopausal women, estrogen deprivation with agents that inhibit aromatase, the critical enzyme in conversion of androgen precursors to estrogen in adipose and breast tissue. Currently underway is the NSABP-P2 trial, the STAR trial, which compares the efficacy and adverse effects of tamoxifen with raloxifene, another SERM not associated with an increased risk of endometrial cancer but with similar risk of thromboembolic disease. Other studies are underway assessing the risks and benefits of aromatase inhibitors in the prevention of breast cancer in high-risk postmenopausal women.