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 ( Quest Diagnostics also has an online quiz for patients to help determine if they are at increased risk of hereditary cancer (

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 

Local genetic counselors can be found by visiting the National Society of Genetic Counselors website (
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 
Breast Cancer Risk Factors

Some of the risk factors for breast cancer that all women should be aware of include2

  • Age: being over 50
  • Menstruation: starting < age 12
  • Menopause: starting > age 55
  • Dense breasts
  • Previous treatment with radiation therapy to the chest
  • Diet and lifestyle: smoking, excessive alcohol, physical inactivity, overweight
  • Family history: close relatives with certain types of cancer
The risk of having a gene variant associated with hereditary breast cancer is higher in individuals with3-5

  • A personal or family history of
  • Breast cancer < age 50
  • Cancer involving both breasts
  • A BRCA-related cancer (ie, breast, ovarian, pancreatic, prostate)
  • A rare cancer, such as sarcoma
  • A male family member with breast cancer
  • Multiple family members with breast cancer
  • An Ashkenazi Jewish ethnicity 

How the Laboratory Can Help

Quest offers the BRCA Panel to test for variants in the 2 high-risk genes (BRCA1, BRCA2) predominantly associated with breast cancer. In addition, Quest offers the BRCA Panel Plus (7 genes) test, which tests for 5 genes in addition to BRCA1 and BRCA2: CDH1, PALB2, PTEN, STK11, and TP53. These genes are associated with a high risk for breast cancer, are clinically actionable, and have management guidelines.4 For people of Ashkenazi Jewish decent, Quest offers the BRCA Ashkenazi Jewish Screen for the 3 BRCA variants commonly found in this population. 

Quest also offers:
  • The Hereditary Breast Cancer Panel (16 genes), which tests for variants in BRCA1, BRCA2, 9 other genes associated with breast cancer, and 5 genes associated with ovarian, uterine, colon, and other Lynch-syndrome related cancers.
  • The Guideline-Based Hereditary Cancer Panel (32 genes), which tests for variants in BRCA1 and BRCA2 and 30 other genes that are associated with moderate and high risk for common cancers, such as breast, colon, prostate, uterine (endometrial), ovarian, and pancreatic cancers, as well as melanoma. All the genes in this panel have management guidelines and are considered clinically actionable.4
  • The Comprehensive Hereditary Cancer Panel, which tests for variants in 66 genes. This test evaluates genes associated with a broad spectrum of hereditary cancers, including common cancers and less common cancers, such as neuroendocrine tumors. Some of the genes are associated with moderate to high risk for certain cancers and are clinically actionable, with established management guidelines. Other genes are emerging; these genes have been associated with risk for certain cancers, but the actual risk may not be well-defined and management guidelines have not been established.

Board-certified genetic counselors are also available for consultation with healthcare providers at 1.866.GENE.INFO (1.866.436.3463) or at

Quest also offers webinars to aid in understanding genetic testing for hereditary cancers. They are available at

Quest will verify insurance coverage of the test. If the patient’s estimated out-of-pocket cost is more than $100, the patient or the provider will be notified before testing is performed. Financial assistance may be available for qualified low-income patients. Please visit for more details.

Please complete the form below to recieve the latest updates.

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590
  2. What are the risk factors for breast cancer? Centers for Disease Control and Prevention. Reviewed September 11, 2018. Accessed July 22, 2020.
  3. BRCA mutations: cancer risk and genetic testing. National Cancer Institute. Reviewed January 30, 2018. Accessed July 22, 2020.
  4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 1.2020. Updated December 4, 2019. Accessed July 22, 2020.
  5. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33(31):3660-3667. doi:10.1200/JCO.2015.63.0996
  6. US Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. US Preventive Services Task Force recommendation statement. JAMA. 2019;322(7):652-665. doi:10.1001/jama.2019.10987
  7. Kurian AW, Li Y, Hamilton AS, et al. Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol. 2017;35(20):2232-2239. doi:10.1200/JCO.2016.71.6480
  8. Childers CP, Childers KK, Maggard-Gibbons M, et al. National estimates of genetic testing in women with a history of breast or ovarian cancer. J Clin Oncol. 2017;35(34):3800-3806. doi:10.1200/JCO.2017.73.6314
  9. FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer genes. United States Food and Drug Administration. Published March 6, 2018. Updated March 7, 2018. Accessed July 30, 2019.

Content reviewed 10/2020