Breast and Ovarian Cancer Genes

Several genes are associated with an increased risk for breast and ovarian cancer. The two most common are called BRCA1 and BRCA2. If either of these genes are inherited in a changed or damaged form, it can cause an increased risk for cancer. Damage or changes in the genes are called mutations. Mutations in BRCA1 or BRCA2 increases the risk for breast, ovarian, pancreatic, and male breast cancer. Other cancer risks such as prostate, melanoma, and gallbladder, and colon are still being researched.

BRCA1 and BRCA2 Function and Inheritance

BRCA1 and BRCA2 are called tumor suppressor genes. Their role is to make sure damage that naturally occurs over time inside a cell is repaired. By repairing this damage, these genes protect us against breast and ovarian cancer. We inherit two copies of BRCA1 and two copies of BRCA2. As long as one copy of these genes is working normally, cancer can be suppressed and will not likely develop in a cell. If both copies of the gene in a pair are mutated, the BRCA gene cannot complete the necessary repairs that a cell needs to prevent cancer. People who inherit a mutation on one copy of BRCA1 or BRCA2 from either parent are more likely to develop cancer than the general population. This is because they begin life with only one working copy of the gene and therefore have no "backup" copy like most people in case the gene is damaged due to the natural aging process, environmental exposures, and unknown causes.

Genetic Testing for Hereditary Breast and Ovarian Cancer Syndrome

Genetic testing is performed on DNA found in our blood or cheek cells of our saliva. The testing process identifies the BRCA1 and BRCA2 genes and checks them for any changes that may affect the function of the gene. As we discussed, these changes that prevent the correct function of the gene are called mutations. Sometimes gene changes are found that do not affect how the well the gene works. These changes are called variants or polymorphisms. The first person in the family to be tested will have both BRCA1 and BRCA2 evaluated. If a mutation is found in one family member, other family members may pursue testing specifically for that same mutation.

There are three possible outcomes for genetic testing of BRCA1 and BRCA2:

  1. Positive result (a mutation is detected)
    A positive result gives a diagnosis of Hereditary Breast and Ovarian Cancer (HBOC). If a mutation is detected, this provides information to your family that can influence cancer detection and prevention strategies. Please refer to the surveillance and surgery options listed below for more details. In addition, relatives who are not found to have the mutation can forgo earlier and increased surveillance programs, but still face the same cancer risks as the general population.
  2. Negative result (no mutation is detected)
    If a mutation is not detected, this greatly reduces the chance that you have a BRCA mutation but cannot eliminate the possibility entirely. It does not always mean that a cancer susceptibility gene can be ruled out in your family. In some cases, there may be a genetic change in a gene that cannot be detected with the current technology or there may be another gene created cancer risk that has not been tested or even discovered yet. We will discuss any available additional testing for your family should this situation occur.
  3. Uncertain Variant (results are inconclusive)
    Sometimes, the results of genetic testing are inconclusive or unclear. This occurs when a change is detected in the DNA but it cannot be determined if the change can cause increased cancer risk or if it is a harmless change due to normal human variation. While there are some methods available to try and clarify whether these uncertain gene alterations are linked with increased cancer risks, the answer may not be determined in the near future.

Cancer Risks in Families with BRCA mutations

Lifetime risks for breast cancer for women in an average risk population are 1 in 8, or 13%. The lifetime risk for breast cancer in women with a BRCA1 or BRCA2 mutation is between a 50-85%. Some research suggests that 85% may be an overestimate in some families. Without intervention (such as surgery or medication to lower risk, there is a 40-60% chance to develop a new breast cancer unrelated to the first diagnosis in the future.

Approximately 1 in 70, or 1-2%, of women in an average risk population develops ovarian cancer during their lifetime. The lifetime risk for ovarian cancer for a woman who inherits BRCA1 mutation is approximately 25-45%. Ovarian cancer occurs less frequently in women with BRCA2 mutation, as the lifetime risk appears to be closer to the 20% range. However, this risk is still high enough that the same recommendations are made for a woman with a BRCA1 or BRCA2 mutation (see below).

Male breast cancer has been observed in men who have mutations in BRCA1 and BRCA2. It is estimated that a man with a BRCA1 or BRCA2 mutation has about a 2-6% lifetime chance to develop breast cancer. Although this risk may seem low, it is a considerable increase compared to men in the general population who have closer to a 1 in 1,000 or 0.1% risk for breast cancer. Men with mutations may also have an increased lifetime risk to develop prostate cancer or a risk to develop it at a younger age.

As mentioned previously, people with BRCA mutations may be at increased risk for other cancers. These include cancers of the pancreas, colon, gallbladder, and malignant melanoma. Additional research is needed to clarify cancer risks and management in people with inherited mutations in BRCA1 and BRCA2.

Surveillance and Prevention

Breast cancer surveillance for women with documented mutations in BRCA1 or BRCA2, current recommendations include mammograms and breast ultrasound every 12 months beginning between age 20-25. This is earlier than the recommendations for the general population that suggest beginning annual mammography at age 40. Breast MRI is also suggested every 12 months and is usually scheduled 6 months after mammogram so breast tissue is imaged twice a year. Clinical breast exams should be performed by a health care professional every 6-12 months beginning in the early 20s, and it is recommended that breast self-exams be performed monthly starting at age 18.

Men with BRCA1 or BRCA2 mutations should consider having breast exams performed by a doctor, perform breast self-exams at home, and may even have mammograms.

Ovarian cancer surveillance, including pelvic exams, transvaginal ultrasounds, and CA-125 levels may be recommended every 6-12 months for women with BRCA1 or BRCA2 mutations between ages 25-35. However, these techniques have not been proven to be reliable in detecting ovarian cancer so such screening is decided at the discretion of the physician in conjunction with the wishes of the individual patient.

Prostate cancer surveillance, including annual digital rectal exams and Prostate Serum Antigen (PSA) blood test are recommended for male BRCA1 and BRCA2 mutation carriers and may be covered by insurance at an earlier age. Digital rectal examinations should be initiated by age 40 and PSA testing conducted annually by age 50.


Prophylactic surgery is the removal of at-risk tissue and organs before cancer develops and is an option for people with BRCA1 or BRCA2 mutations.

Research indicates that prophylactic mastectomy reduces the risk of developing breast cancer by 90% in women with mutations.

Prophylactic bilateral salpingo-oophorectomy (BSO), or removal of the fallopian tubes and ovaries, is an option for women with mutations – especially after childbearing is completed or by age 40. This surgery eliminates the risk of ovarian cancer, but not the risk of an ovarian-related cancer that may occur in the peritoneum (the tissue that lines the abdominal cavity where the ovaries are located). The chances that a woman with a BRCA2 mutation will develop peritoneal cancer after an oophorectomy are very low. Preliminary evidence also suggests that prophylactic oophorectomy in premenopausal women with BRCA2 mutations may also reduce the risk of breast cancer. Once the ovaries are removed, a woman becomes menopausal. The option of total abdominal hysterectomy (TAH), or removal of the uterus, in addition to the BSO, may be discussed with a physician.

Produced by The West Clinic and Methodist Healthcare

Follow these links to the National Society of Genetic Counselors to find more helpful information: