If a woman tests positive for a BRCA1 or BRCA2 mutation, health professionals may offer her the following options alone or in combination:
Women who test positive for a BRCA1 or BRCA2 mutation may be encouraged to get clinical breast exams, mammograms, ultrasounds, and other screening tests several times a year starting at age 35 or earlier. However, there is no proof that vigilant surveillance and screening save the lives of BRCA1 and BRCA2 mutation carriers or even that they detect cancers earlier.
We do not know the long-term impact of frequent mammography on cancer risk in BRCA1 and BRCA2 carriers. It has been hypothesized that the radiation from frequent mammography actually may harm women with mutations in these two genes since they are involved in DNA repair caused by radiation damage (this means that, when BRCA1 and BRCA2 are working properly, they help to protect cells from the effects of radiation).
Whether screening with mammography benefits any women, particularly women under the age of 50, is controversial. Mammograms are less accurate in younger women than in older women because younger women have denser breast tissue. Some data indicate that magnetic resonance imaging (MRI) may be more accurate at detecting breast cancer in BRCA1 and BRCA2 mutation carriers than mammography (Warner et al, 2001). However, no screening tools have been shown to reduce the risk of dying from breast cancer in this population of women.
Studies suggest that the drug tamoxifen reduces the five-year risk of breast cancer in high-risk women. However, it is still unknown whether tamoxifen can reduce breast cancer risk specifically in women who carry a BRCA1 or BRCA2 mutation. Some studies indicate that BRCA1 mutations are associated with predominantly estrogen receptor-negative breast cancers (Vaziri et al, 2001). It has been hypothesized that tamoxifen would not benefit BRCA1 mutation carriers because tamoxifen only reduces the risk of estrogen receptor-positive breast cancers. One study suggests that tamoxifen actually may increase breast cancer risk in BRCA1 mutation carriers, but decrease risk in BRCA2 mutation carriers (King et al, 2001). However, this study was very small so the results may not be reliable.
No studies have examined whether tamoxifen reduces the overall death rate in women at high risk for breast cancer. It has been known for some time that tamoxifen use increases the risk of several life-threatening diseases, including endometrial cancer, stroke, and venous thromboembolic disease. New data indicate that tamoxifen also increases the risk of uterine sarcoma, a rare and aggressive uterine cancer. The U.S. Preventive Services Task Force recently issued recommendations suggesting that the benefits of tamoxifen may not outweigh the risks in many women who take the drug to reduce their risk of breast cancer.
Women without breast cancer who test positive for a BRCA1 or BRCA2 mutation may choose to undergo a bilateral prophylactic mastectomy. This procedure is the surgical removal of both breasts in order to reduce the risk of getting breast cancer. Women who have been diagnosed with breast cancer and who test positive for a BRCA1 or BRCA2 mutation may choose to undergo a mastectomy (removal of the affected breast) and/or a prophylactic mastectomy of the contralateral breast. These procedures may reduce the risk of getting breast cancer a second time. One study suggests that prophylactic mastectomy can reduce breast cancer risk by at least 90% in women with a family history of the disease (Hartmann, 1994). Another smaller study suggests that this surgery can reduce breast cancer risk to the same extent in BRCA1 and BRCA2 mutation carriers (Hartmann et al, 2001).
Women who test positive for a BRCA1 or BRCA2 mutation also may choose to have a bilateral prophylactic oophorectomy. This procedure is the surgical removal of both ovaries in women who do not have cancer. Some evidence indicates that bilateral prophylactic oophorectomy reduces the risk of ovarian cancer by 96%. Several studies suggest that this surgery also can reduce the risk of breast cancer by about 50-70% in BRCA1 and BRCA2 mutation carriers after 10 years of follow-up (Rebbeck 1999, 2001). This effect is probably due to the fact that removing a woman's ovaries decreases her exposure to estrogen, and estrogen exposure is a risk factor for breast cancer.
Although prophylactic mastectomies and prophylactic oophorectomies may achieve large reductions in cancer risk, no studies have examined whether these procedures reduce the risk of dying from breast or ovarian cancer. It is important to note that these two drastic operations do not remove all breast and ovarian tissue, and some women may still get breast cancer and/or ovarian cancer in the remaining tissue. In addition, the most appropriate age for a woman to get these surgeries is still unknown. By the time a woman chooses to undergo a prophylactic mastectomy or oophorectomy, she may have some undetected cancer that has already spread beyond the breast or ovaries. In such a case, prophylactic surgeries will not improve her chance of survival.
Prophylactic surgeries have both emotional and physical risks that must be carefully weighed against the potential benefits. In particular, pre-menopausal women who have bilateral oophorectomies will lose their ability to have children and will undergo early menopause. They also may be at increased risk for heart disease and sexual dysfunction. Like most major surgical procedures, complications can occur during and after prophylactic mastectomies and prophylactic oophorectomies.
Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999;340(2):77-84.
Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001;93(21):1633-7.
King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 2001;286(18):2251-6.
Warner E, Plewes DB, Shumak RS, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 2001;19(15):3524-31.
Vaziri SA, Krumroy LM, Elson P, et al. Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at diagnosis. Clin Cancer Res 2001;7(7):1937-45.
Rebbeck TR, Levin AM, Eisen A, et al. Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 1999;91(17):1475-9.
Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616-22.