BRCA1 and BRCA2 Genes: What You Need to Know
Massachusetts General Hospital Cancer Center
Jews of central and eastern European descent have a one in forty chance of having a mutation in their BRCA1 or BRCA2 gene that puts them at much higher risk than the general population of developing ovarian cancer, breast cancer (male or female) and prostate cancer.
How can a person who has a BRCA1 or BRCA2 gene mutation manage their risk of cancer?
According to the NIH's National Cancer Institute, "several options are available for managing cancer risk in individuals who have a known BRCA1 or BRCA2 mutation. These include enhanced screening, prophylactic (risk-reducing) surgery, and chemoprevention.
Enhanced Screening. Some women who test positive for BRCA1 and BRCA2 mutations may choose to start cancer screening at younger ages than the general population or to have more frequent screening. For example, some experts recommend that women who carry a harmful BRCA1 or BRCA2 mutation undergo clinical breast examinations beginning at age 25 to 35 years. And some expert groups recommend that women who carry such a mutation have a mammogram every year, beginning at age 25 to 35 years.
Enhanced screening may increase the chance of detecting breast cancer at an early stage, when it may have a better chance of being treated successfully. Women who have a positive test result should ask their health care provider about the possible harms of diagnostic tests that involve radiation (mammograms or x-rays).
Recent studies have shown that MRI may be more sensitive than mammography for women at high risk of breast cancer. However, mammography can also identify some breast cancers that are not identified by MRI, and MRI may be less specific (i.e., lead to more false-positive results) than mammography. Several organizations, such as the American Cancer Society and the National Comprehensive Cancer Network, now recommend annual screening with mammography and MRI for women who have a high risk of breast cancer.
No effective ovarian cancer screening methods currently exist. Some groups recommend transvaginal ultrasound, blood tests for the antigen CA-125, and clinical examinations for ovarian cancer screening in women with harmful BRCA1 or BRCA2 mutations, but none of these methods appears to detect ovarian tumors at an early enough stage to reduce the risk of dying from ovarian cancer. For a screening method to be considered effective, it must have demonstrated reduced mortality from the disease of interest. This standard has not yet been met for ovarian cancer screening.
The benefits of screening for breast and other cancers in men who carry harmful mutations in BRCA1 or BRCA2 is also not known, but some expert groups recommend that men who are known to carry a harmful mutation undergo regular mammography as well as testing for prostate cancer. The value of these screening strategies remains unproven at present.
Prophylactic (Risk-reducing) Surgery. Prophylactic surgery involves removing as much of the "at-risk" tissue as possible. Women may choose to have both breasts removed (bilateral prophylactic mastectomy) to reduce their risk of breast cancer. Surgery to remove a woman's ovaries and fallopian tubes (bilateral prophylactic salpingo-oophorectomy) can help reduce her risk of ovarian cancer. Removing the ovaries also reduces the risk of breast cancer in premenopausal women by eliminating a source of hormones that can fuel the growth of some types of breast cancer.
No evidence is available regarding the effectiveness of bilateral prophylactic mastectomy in reducing breast cancer risk in men with a harmful BRCA1 or BRCA2 mutation or a family history of breast cancer. Therefore, bilateral prophylactic mastectomy for men at high risk of breast cancer is considered an experimental procedure, and insurance companies will not normally cover it.
Prophylactic surgery does not completely guarantee that cancer will not develop because not all at-risk tissue can be removed by these procedures. Some women have developed breast cancer, ovarian cancer, or primary peritoneal carcinomatosis (a type of cancer similar to ovarian cancer) even after prophylactic surgery. Nevertheless, the mortality reduction associated with this surgery is substantial: Research demonstrates that women who underwent bilateral prophylactic salpingo-oophorectomy had a nearly 80 percent reduction in risk of dying from ovarian cancer, a 56 percent reduction in risk of dying from breast cancer, and a 77 percent reduction in risk of dying from any cause.
Emerging evidence suggests that the amount of protection that removing the ovaries and fallopian tubes provides against the development of breast and ovarian cancer may be similar for carriers of BRCA1 and BRCA2 mutations, in contrast to earlier studies.
Chemoprevention. Chemoprevention is the use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the recurrence of, cancer. Although two chemopreventive drugs (tamoxifen and raloxifene) have been approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of breast cancer in women at increased risk, the role of these drugs in women with harmful BRCA1 or BRCA2 mutations is not yet clear.
Data from three studies suggest that tamoxifen may be able to help lower the risk of breast cancer in BRCA1 and BRCA2 mutation carriers, including the risk of cancer in the opposite breast among women previously diagnosed with breast cancer. Studies have not examined the effectiveness of raloxifene in BRCA1 and BRCA2 mutation carriers specifically.
Oral contraceptives (birth control pills) are thought to reduce the risk of ovarian cancer by about 50 percent both in the general population and in women with harmful BRCA1 or BRCA2 mutations. (2)"
(1) http://www.facingourrisk.org/understanding-brca-and-hboc/information/finding-health-care/paying_for_testing/basics/insurance_coverage_for_testing.php#text accessed on May 31, 2017
(2) https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#q12 accessed on May 20, 2017