Hormonal therapy has been used for chemoprevention in individuals at high risk for breast cancer. Overall it is recommended only in very special circumstances. In 2002, a clinical practice guideline by the US Preventive Services Task Force (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.

Selective estrogen receptor modulators (SERMs)

The guidelines were based on studies of SERMs from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction for raloxifene was 76%. The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride on the prevention of prostate cancer, in which only low-grade prostate cancers were prevented). The Italian trial showed benefit from tamoxifen.

Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen. In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene. The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke". On September 14, 2007, the US Food and Drug Administration approved raloxifene (Evista) to prevent invasive breast cancer in postmenopausal women.

Endocrine disruptors

Many xenoestrogens (industrially made estrogenic compounds) and other endocrine disruptors are potential risk factors of breast cancer.

Diethylstilbestrol (DES) is a synthetic form of estrogen. It has been used between the early 1940s and 1971. Pregnant women took DES to prevent certain pregnancy complications. However, it also increased their risk of breast cancer. It also increased the risk of breast cancer in the prenatally exposed daughters after they have reached an age 40 years.

Furthermore, there is exposure to endocrine disruptors from the environment, in addition to phytoestrogens mentioned above in the diet section. See xenoestrogens in environmental factors below