RISK REDUCTION OPTIONS FOR WOMAN

What are the cancer risk reduction options for women who are at increased risk of breast cancer but not at the highest risk?

Risk-reducing surgery is not considered an appropriate cancer prevention option for women who are not at the highest risk of breast cancer (that is, for those who do not carry a high-penetrancegene mutation that is associated with breast cancer or who do not have a clinical or medical history that puts them at very high risk). However, some women who are not at very high risk of breast cancer but are, nonetheless, considered as being at increased risk of the disease may choose to use drugs to reduce their risk.

Health care providers use several types of tools, called risk assessment models, to estimate the risk of breast cancer for women who do not have a deleterious mutation in BRCA1, BRCA2, or another gene associated with breast cancer risk. One widely used tool is the Breast Cancer Risk Assessment Tool (BRCAT), a computer model that takes a number of factors into account in estimating the risks of breast cancer over the next 5 years and up to age 90 years (lifetime risk). Women who have an estimated 5-year risk of 1.67 percent or higher are classified as "high-risk," which means that they have a higher than average risk of developing breast cancer. This high-risk cutoff (that is, an estimated 5-year risk of 1.67 percent or higher) is widely used in research studies and in clinical counseling.

Two drugs, tamoxifen and raloxifene, are approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of breast cancer in women who have a 5-year risk of developing breast cancer of 1.67 percent or more. Tamoxifen is approved for risk reduction in both premenopausal and postmenopausal women, and raloxifene is approved for risk reduction in postmenopausal women only. In large randomized clinical trials, tamoxifen, taken for 5 years, reduced the risk of invasive breast cancer by about 50 percent in high-risk postmenopausal women; raloxifene, taken for 5 years, reduced breast cancer risk by about 38 percent in high-risk postmenopausal women. Both drugs block the activity of estrogen, thereby inhibiting the growth of some breast cancers. The US Preventive Services Task Force (USPSTF) recommends that women at increased risk of breast cancer talk with their health care professional about the potential benefits and harms of taking tamoxifen or raloxifene to reduce their risk .

Another drug, exemestane, was recently shown to reduce the incidence of breast cancer in postmenopausal women who are at increased risk of the disease by 65 percent. Exemestane belongs to a class of drugs called aromatase inhibitors, which block the production of estrogen by the body. It is not known, however, whether any of these drugs reduces the very high risk of breast cancer for women who carry a known mutation that is strongly associated with an increased risk of breast cancer, such as deleterious mutations in BRCA1 and BRCA2.

Some women who have undergone breast cancer surgery, regardless of their risk of recurrence, may be given drugs to reduce the likelihood that their breast cancer will recur. (This additional treatment is called adjuvant therapy.) Such treatment also reduces the already low risks ofcontralateral and second primary breast cancers. Drugs that are used as adjuvant therapy to reduce the risk of breast cancer after breast cancer surgery include tamoxifen, aromatase inhibitors, traditional chemotherapy agents, and trastuzumab.