This patient with atypical ductal hyperplasia (ADH) should be offered breast cancer chemoprophylaxis, with exemestane being the most effective agent for postmenopausal women. ADH is a breast lesion associated with an increased risk of development of breast cancer. Studies have shown a three- to fivefold increased risk of breast cancer after a diagnosis of ADH, with a cumulative incidence at 30 years of 35%. Patients with ADH are candidates for breast cancer chemoprophylaxis. Among the available chemoprophylactic agents, exemestane is associated with the greatest reduction in breast cancer risk. Exemestane is an aromatase inhibitor that prevents conversion of androgens to estrogens and profoundly suppresses estrogen levels in postmenopausal women. The National Cancer Institute of Canada's Exemestane Prophylaxis Study compared administration of exemestane for 5 years with administration of placebo for the same period in patients with a 5-year risk of breast cancer of at least 1.67%. Patients with ADH were included in this study. At a median follow-up of 3 years, there was a 65% relative reduction in the annual incidence of invasive breast cancer in patients taking exemestane. Toxicities included a low incidence of grade 3 arthralgia and hot flushes. There was no difference in the incidence of skeletal fractures or development of osteoporosis, cardiovascular events, or other cancers in patients taking either exemestane or placebo.

Alternate chemoprophylaxis options include tamoxifen and raloxifene. Tamoxifen decreases the risk of breast cancer by 49% though it has a 0.1% risk per year of endometrial cancer and a 1% risk of vascular events including venous thrombosis and strokes. Raloxifene does not increase the risk of endometrial cancer and has a 25% lower risk of vascular events. It is less effective than tamoxifen, retaining 76% of the benefit of tamoxifen, but is an option in patients who want to decrease toxicities. All three chemoprophylaxis agents (tamoxifen, raloxifene, and exemestane) can be used in postmenopausal women but only tamoxifen is an option in premenopausal or perimenopausal women.

Vitamin D supplementation is being studied for breast cancer prevention, but any benefits are currently unclear. Some studies have shown a mild decrease in breast cancer risk in persons with normal serum vitamin D levels compared with those having low levels, whereas other studies have found no benefit.

Bilateral prophylactic mastectomy is an option for women with a high risk of breast cancer due to inherited syndromes, such as women with BRCA1/2 mutations, but is not appropriate for women with atypical lesions such as atypical hyperplasia or lobular neoplasia.

Continuing hormone replacement therapy will increase the risk of breast cancer and prevent chemoprophylactic medications such as tamoxifen, raloxifene, and exemestane from decreasing this risk.