Hereditary Breast and Ovarian Cancer Syndrome is caused by mutations (breaks) in the genes BRCA1 and BRCA2. When they are able to function normally, BRCA1 and BRCA2 work together along with other genes in the cell to stop cancer from developing. When these genes are mutated into cancer susceptibility genes, a person has a greater lifetime risk of 4 major types of cancer: breast, ovarian, pancreatic, and prostate. There is also some evidence linking BRCA1/2 mutations to other forms of cancer, such as melanoma (skin cancer), but these data are not conclusive.
Many other recently discovered genes can provide a similar clinical picture to BRCA1/2, because they help BRCA1/2 to stop cancer. These genes, of which there are about a dozen for which we can currently test, are labeled as moderate risk genes and typically have much more mild cancer risks. Having a mutation in one of these genes is not the same as having a mutation in BRCA1 or BRCA2. If you are unclear at any point about what you should do to help yourself stay healthy, please call your doctor or genetic counselor.
Genetic testing can be done to help determine whether a BRCA mutation is present in a family. There have been hundreds of different mutations identified throughout the BRCA genes. Thus, genetic testing involves reading through the entire genetic code of both genes to try and identify if a mutation is present. It is important to remember, however, that there are certain mutations in the BRCA genes that may not be detected by the laboratory techniques being used. It is also possible that a family’s cancer, if hereditary, is due to a mutation in a different cancer susceptibility gene which has not yet been identified. Thus, a negative (or “normal”) BRCA test result does not rule out the possibility that a hereditary cancer syndrome is present in a family
In addition, normal variations can also occur within genes which do not affect the way they function. Unfortunately, it can sometimes be difficult to determine whether a change found in a gene is a normal variation or a mutation that can lead to cancer. Thus it is possible to get an ambiguous result from genetic testing (“variant of uncertain significance”).
We recommend that testing be performed first on someone in the family who has had cancer, since the results obtained from testing an unaffected person first may be difficult to interpret. If a BRCA mutation is found, then other relatives can be tested more easily and with high accuracy.
Whether or not to pursue genetic testing or what genetic testing to undergo is a very personal decision, and one that a person should only make if they fully understand their decision.
Options for Screening and Prevention
Options for people at risk of having a BRCA mutation include careful screening, chemoprevention, and prophylactic surgery.
Individuals with BRCA mutations or at-risk individuals should receive careful cancer screening. The National Comprehensive Cancer Network recommends that women with these mutation be aware of the normal condition of their breasts at age 18 and receive clinical breast exams every 6-12 months beginning at age 25. Imaging, usually annual breast MRIs should also begin at age 25, and between the ages of 35-75, women should receive an annual mammogram and an annual breast MRI, ideally staggered so the breasts are screened every 6 months. Women should also be offered a surgical consultation to review the possibility of a mastectomy (surgical removal of one or both breasts). Screening technologies for ovarian cancer exist, traditionally an ultrasound and a blood test for a certain cancer antigen, CA-125, but they have not been shown to be very effective. Women should consider a risk reducing salpingo-oophrectomy (surgical removal of the ovaries and the fallopian tubes), typically between ages 35-40. For both men and women, no specific screening guidelines for pancreatic cancer are recommended, but the signs and symptoms of this disease should be reviewed. For men, the risk for breast cancer is sufficient to recommend breast awareness and annual clinical exams beginning at age 35. Men should also begin/consider prostate cancer screening at age 45.
In addition to the screening discussed above, individuals with BRCA mutations/at-risk individuals should follow the general American Cancer Society guidelines to screen for other BRCA-related cancers. Having a BRCA mutation does not make it impossible to develop a non-BRCA related cancer.