Genetic Screening for Ovarian and Breast Cancer

Summary
Although breast cancer is common, in most cases we cannot identify a hereditary cause. However, women who have close relatives with breast or ovarian cancer do have more chance of developing these cancers. Blood tests can detect gene changes (mutations) that explain some of this higher risk, in genes called BRCA1 or BRCA2. If mutations are found, then the chances of developing breast or ovarian cancer can be estimated with fair accuracy. If no mutations are found, then it is harder to predict a woman's risk of breast or ovarian cancer, but her risk remains higher than for women from families without these diseases. Each woman should discuss her own and her family’s history with her physician before deciding whether to have BRCA testing.

Women at higher risk of breast and ovarian cancer can take certain steps to find cancer early or reduce the chances of developing cancer. To lower the chance of breast cancer, women may take medication to block estrogen's effect in the breast or have their breasts removed (mastectomy). For women who do not choose mastectomy, yearly mammograms or breast MRI should be performed. To lower the chance of ovarian cancer, high risk woman may take birth control pills for at least 5 years or have their ovaries removed. No screening tests currently available are proven to find ovarian cancer at an early, curable stage.

Breast Cancer
Breast cancer is very common, affecting 1 in 8 American women during their lifetime. While most breast cancers occur in women without a family history of breast cancer, about 10% of breast cancers are found in women with changes (mutations) in genes called BRCA1 or BRCA2. These women have up to 85% chance of developing breast cancer by age 80. (Men with mutations in the BRCA2 gene have a 5% to 10% chance of developing breast cancer.)

Ovarian Cancer
Ovarian cancer affects 1.5% of American women. BRCA1 gene mutations are found in 13% of women with ovarian cancer but in 40% of such women who also have a family history of ovarian cancer.

Current Screening for Breast and Ovarian Cancer
No screening test is perfect, and this is true in breast cancer screening. Current screening options include breast exam, mammogram, and breast MRI. All of these can have "false positives" (finding abnormalities that are not breast cancer) and "false negatives" (missing true breast cancers). For most women, regular film mammogram is our best tool for early breast cancer detection. Breast MRI is recommended for higher risk women with any of the following: 1) BRCA mutation or 2) family history of these mutations, 3) high risk of breast cancer based on family history and other factors, 4) chest radiation between ages 10 and 30, or 5) a rare genetic condition that increases breast cancer risk. Digital mammograms are not proven to be better than standard mammograms at finding breast cancer or pre cancerous changes.

There are currently no reliable ways to screen women for ovarian cancer. Pelvic examinations (feeling the ovaries through the vagina), trans-vaginal ultrasound (viewing the ovaries through a probe inserted in the vagina), and blood tests (CA 125) are not proven to find ovarian cancer early enough to improve outcomes.

How do results of BRCA genetic screening affect management of women without breast cancer?

  • If a family member with breast or ovarian cancer is BRCA positive while the unaffected woman is BRCA negative: then the unaffected woman was lucky not to inherit the abnormal gene, and she carries the same risk of developing breast cancer as other women at "average risk" (about 13% chance of developing breast cancer during her lifetime). Such women should have routine screening for breast cancer.
  • If both the affected relatives and the unaffected woman are BRCA positive: then the unaffected woman may have up to an 85% chance of developing breast or ovarian cancer. Breast screening through breast MRI and mammograms and preventive measures (tamoxifen, mastectomy, or ovary removal) may be considered.
  • If neither the affected relatives nor the unaffected woman are BRCA positive: then risk estimations are less accurate, because the family may carry gene mutations that current technology cannot detect. The chance of developing breast or ovarian cancer may be 55% (depending on the family history). Breast MRI and mammogram should be considered. Preventive measures (tamoxifen, mastectomy, or ovary removal may be recommended.


The following table summarizes how information on BRCA mutation status affects recommendations.

BRCA Mutation Status

Unaffected Woman's Lifetime Risk of Developing Cancer

Recommendations for Unaffected Woman

Unaffected Woman

Affected Relative

Breast Cancer

Ovarian Cancer

Breast MRI & Mammogram

Tamoxifen, Mastectomy, Ovary Removal

-

+

13%

1.5%

No

No

+

+

85%

60%

Yes

Consider Options

-

-

Depends on Family History

Yes

Consider Options



Health insurance concerns about BRCA test results
BRCA test results have not been used as a basis for raising premiums or denying insurance policies for people with group health insurance plans (e.g. through their employer or a professional organization) because of a "pre-existing condition." The Health Insurance Portability and Accountability Act (HIPAA) is intended to guarantee health insurance coverage regardless of health status and pre-existing conditions. HIPAA does not protect people insured under individual (rather than group) insurance plans from being denied insurance or from paying higher premiums because of pre-existing conditions.

Life insurance and BRCA test results
Information about pre-existing medical conditions or risks is used routinely by life insurance underwriters to determine eligibility for coverage and to set premiums. An individual's failure to disclose such information, if known, is illegal. The extent to which such genetic information is being gathered by life insurance companies or used to determine eligibility or premiums is unknown.

References
Armstrong K., Eisen A., and Weber B. Assessing the risk of breast cancer. N. Engl J. Med, 2000; 342(8): 564-571.

Levine A., and Hughes, K.S. Cost effectiveness of the identification of women at high risk for the development of breast and ovarian cancer. In Vogel V.G., (ed.), Management of Women at High Risk for Breast Cancer. Boston: Blackwell Science, Inc. 1998.

American Medical Association. The role of genetic susceptibility testing for breast and ovarian cancer. April 1999.

Koenig, B.A., Greely, H.T., McConnell, L.M., et al. Genetic testing for BRCA1 and BRCA2: Recommendations of the Stanford Program in Genomics, Ethics and Society. J Women’s Health, 1998; 7(5): 531-545.

Burke, W., Daly. M., Garber, J., et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer II, BRCA 1 and BRCA2. JAMA, 1997; 277: 997-1003.

Hartmann, L.C., Schaid, D.J., Woods, J.E., et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med, 1999; 340: 77-84.

Fisher, B., Costantino, J.P., Wickerham, D.L., et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl Cancer Inst, 1998; 990:1371-88.

Narod, S.A., Risch, H., Moshehi, R., et al. Oral contraceptives and the risk of hereditary ovarian cancer. N. Engl J Med., 1998; 339:424-428.

Last revised August 2009