Hereditary Breast Cancer
Breast cancer is the most common type of cancer and the second leading cause of cancer death for women in the United States.1 Fortunately, breast cancer can be treated and most women survive.1 Early diagnosis begins with identifying individuals with common risk factors (see Sidebar), including family history.2 In fact, approximately 5% to 10% of breast cancer cases are hereditary.3 Genetic testing can identify women (and men) who are at increased risk for hereditary breast cancer (see Sidebar). Individuals at increased risk may benefit from more frequent surveillance or from treatments, such as prophylactic mastectomy.3,4
This article will discuss hereditary breast cancer, and how genetic testing can be used to assess risk.
Genes Associated With Hereditary Breast Cancer
Inherited variants in the breast cancer susceptibility 1 and 2 genes (BRCA1 and BRCA2) increase the risk of breast cancer, and account for 20% to 25% of hereditary breast cancers.3 Other genes associated with hereditary breast cancer include ATM, BARD1, BRIP1, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, and TP53.4
Assessing Risk
Professional organizations recommend that primary care providers assess whether women or men are at increased risk of having mutations in BRCA1 or BRCA2 based on personal or family history.3-5 The latest update to the United States Preventive Services Task Force (USPSTF) guidelines expands the population that should be assessed based on personal or family history.6 These guidelines now include women considered cancer-free who have been previously treated for breast, ovarian, peritoneal, or tubal cancers.6 In addition, ancestry associated with BRCA1/2 (founder) gene mutations is more explicitly included as a risk factor.6
Tools to help assess risk include the National Cancer Institute Breast Cancer Risk Assessment Tool, commonly known as the Gail model (BCrisktool.cancer.gov). Quest Diagnostics also has an online quiz for patients to help determine if they are at increased risk of hereditary cancer (QuestHereditaryCancer.com).
Genetic Counseling and Testing
Genetic counseling is a critical component of the cancer risk assessment. The National Comprehensive Cancer Network® (NCCN) recommends that a genetic counselor, or a healthcare professional with experience in cancer genetics, provide counseling throughout the testing process.4 However, many patients undergoing genetic testing do not receive adequate counseling regarding the risks or benefits prior to testing, as well as interpreting the results and making treatment decisions after testing.7
Genetic testing is recommended when (1) there is a personal or family history suggesting genetic cancer susceptibility; (2) the test can be adequately interpreted; and (3) the results will aid in the diagnosis or influence the medical or surgical management of the patient or family members at risk for hereditary cancer.4 Individuals with test results indicating the presence of breast cancer-associated variants may also be at risk for other cancers, such as ovarian, pancreatic, or prostate cancer.3,4 Unfortunately, only 20% of women who meet the criteria for hereditary breast cancer testing have been tested and <20% of women with a history of breast or ovarian cancer have received genetic testing or discussed genetic testing with a healthcare provider.8
Men with BRCA1 or BRCA2 mutations are also at increased risk of breast cancer; men with a BRCA2 mutation have a lifetime risk of breast cancer of 7% to 8%, as compared to approximately 0.1% for men with no mutations.4 The NCCN recommends mutation testing for men who have had breast cancer, and for those with certain personal and family medical histories.4
Multigene Testing
Next-generation sequencing (NGS) technology allows the simultaneous analysis of sets of genes associated with a specific family cancer phenotype or multiple phenotypes.4 Because an individual or family may have >1 inherited cancer syndrome, testing with a multigene panel may increase the efficiency of detecting pathogenic variant(s) that impact medical management.4 On the other hand, multigene panels are also more likely to identify less established variants that have not been classified as pathogenic or benign. Although some of these variants may be classified as potentially pathogenic, based on available information, there are no clear guidelines on risk management for carriers of such variants.4
Direct-to-Consumer Genetic Testing
Direct-to-consumer testing for BRCA mutations, as well as for mutations in other genes associated with various cancers, is currently available to individuals. As part of ancestry information, some companies provide BRCA gene mutation status based on microarray single nucleotide polymorphism (SNP) testing. However, this type of direct-to-consumer testing has not been validated for clinical use and generally does not provide genetic risk assessment.4 The NCCN does not recommend changes to a patient’s medical management based solely on direct-to-consumer testing results.4 The Food and Drug Administration (FDA) recommends that direct-to-consumer BRCA test results should not guide treatment; patients should have genetic counseling and confirmatory testing before any treatment decision is made.9
How Healthcare Providers Can Help
Healthcare providers can identify patients at risk for hereditary breast cancer by taking a thorough personal and family history. Individuals at increased risk for hereditary breast cancer may be referred to a genetic counselor or provided with information regarding genetic testing. Appropriate testing can help ensure timely interventions that can improve survival.5
For women at increased risk of hereditary breast cancer, some of the options to reduce the risk for breast cancer include3
- Increased surveillance breast examinations (eg, mammography, magnetic resonance imaging)
- Chemoprevention medications such as tamoxifen
- Surgery such as prophylactic/risk-reducing mastectomy