Genetic Screening for Breast Cancer Provides Answers

While only 5-10% of all cancers have an inherited, genetic component, there are DNA tests available to diagnose gene mutations that put women at a significantly increased risk for breast cancer. Programs like the Froedtert & Medical College Cancer Genetics Screening Program offer genetic counseling and testing to individuals who may be at increased risk of breast cancer based on their personal or family history of cancer.

The genes, known as BRCA1 and BRCA2, hold the key to genetic testing for breast cancer. Mutations of these genes account for about 80% of inherited breast cancers, and also signal an increased risk of ovarian cancer.

Genetic testing requires only a small blood sample from the patient. However, the test itself involves sophisticated molecular techniques in which DNA is extracted from white blood cells and is then sequenced. Only one laboratory in the nation (located in Salt Lake City) conducts full DNA sequencing. Average turnaround time is three to four weeks. The cost is about $2600, plus about $150 for genetic counseling. Insurance coverage is variable depending on the policy and medical history of the individual seeking testing.

Genetic Counseling is Crucial
Before DNA testing is performed, all patients undergo pre-test genetic counseling. Pre-test counseling involves assessment of the patient's personal and family medical history, education about basic genetics and cancer genetics and risk, and an in-depth discussion of the risks, benefits and limitations of testing. At the counseling sessions, misconceptions about breast and ovarian cancer risks are addressed. Sometimes patients believe they are at a much higher risk of cancer than they actually are.

Risk assessment is based on family history, including cousins, aunts, uncles and grandparents, and medical records are obtained documenting cancer cases when possible. Risk factors for hereditary breast cancer include multiple cases of breast or ovarian cancer on one side of the family; cancer at an early age; cancer in both breasts, or breast and ovarian cancer, in the same individual; and male breast cancer. Patients of Ashkenazi Jewish ethnicity are at increased risk, as well. There are other risk factors for breast cancer such as bearing a first child after age 30 or never having had a child. But for someone with a family history suggestive of hereditary cancer, family history can overshadow such risk factors.

Ideally, genetic testing will begin with a family member who has cancer to identify if he or she carries a BRCA1 or BRCA2 mutation, which, therefore, is the likely cause of cancer in the family. If a healthy family member then tests negative for the mutated gene, her breast cancer risk is considered to be that of a woman in the general population: 12% lifetime risk of developing breast cancer and a 1-2 percent lifetime risk of developing ovarian cancer. If a healthy family member tests positive for the gene mutation identified in her family, she has a 60-80% lifetime risk of developing breast cancer and a 20-40% lifetime risk of developing ovarian cancer.

If a patient tests positive for a gene mutation, she will be followed more closely. Instead of an annual mammogram after age 40, she may begin annual mammograms 10 years before the age of breast cancer onset in her relatives, in addition to a monthly self-exam and annual clinical breast exam. Annual ovarian cancer screening may be recommended, including a transvaginal ultrasound and CA125 blood test. Some women may choose to have their breasts and/or ovaries removed while still healthy as a preventive measure. Others may begin taking tamoxifen, a drug to prevent breast cancer.

Impact of Genetic Testing
Genetic testing involves very personal decisions. Some patients feel empowered by knowing their genetic risk, while others prefer not to know or don't feel the additional information will be helpful.

Genetic counseling helps patients prepare for DNA test results and understand the psychological impact test results may have on their family and relationships. Some patients testing positive for a gene mutation may actually feel relief that the cause of breast cancer in their family has been identified and they have a diagnosis that can be dealt with. Some patients may require psychological counseling to address cancer fears. Others may be concerned about passing along the gene to their children. Some might be worried about insurance or job discrimination based on the diagnosis, although no such cases have yet been reported.

Testing negative for a gene mutation may provide relief, but it may even provide disappointment, as the cause of a family's breast cancers remains unknown. There may even be "survivor guilt," as one family member may feel guilty about not carrying a gene mutation while another does.

While genetic testing is not for everyone, the information provided in the counseling process is valuable for all patients.

Mary Ann Gilligan, MD, MPH
Assistant Professor of Medicine, Medical College of Wisconsin
Froedtert and Medical College Cancer Center
Zablocki V.A. Medical Center

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.