Hereditary Breast and Ovarian Cancer Syndrome

Clinical Features

Hereditary breast and ovarian cancer syndrome (HBOC) is an adult-onset, cancer predisposition syndrome. HBOC is characterized by a high risk of breast and ovarian cancers, and an increased risk of other cancers such as male breast cancer, prostate, pancreatic, and melanoma. Individuals with HBOC tend to develop cancer at an earlier age than the general population, and have higher risk for bilateral breast cancer, a second primary tumor in a different tissue, and cancer recurrence. HBOC is not associated with any unique physician exam findings.

Absolute Lifetime Cancer Risks Associated with HBOC

Cancer Type



General Population





Male Breast

















No increase



 *prostate cancer risks for BRCA1/2 carriers by age 65

Prevalence of HBOC

About 5-10% of breast cancers and 10-15% of ovarian cancers can be attributed to HBOC. In the Ashkenazi Jewish population, up to 25% of ovarian cancer can be attributed to HBOC. An estimated 1 in 500-1,000 individuals in the general population have a disease-causing BRCA1 or BRCA2 mutation. About 1 in 40 individuals of Ashkenazi Jewish ancestry carry a BRCA1 or BRCA2 mutation. Statistical algorithms are available to determine the likelihood of a BRCA1 or BRCA2 mutation based on personal and family history.


Identification of a mutation in BRCA1 or BRCA2 by genetic testing is sufficient for the diagnosis of HBOC. Criteria have been developed to identify individuals who would most benefit from genetic testing, based on red flags in the personal and family cancer history. Generally this includes:

  • A known mutation in a cancer susceptibility gene in the family
  • Breast cancer diagnosed 45 y
  • Breast cancer diagnosed >45 with family history of related cancers
  • Triple negative breast cancer diagnosed 60 y
  • 2 primary tumors in the breast
  • Ashkenazi Jewish ancestry and breast or pancreatic cancer at any age
  • Ovarian cancer (including Fallopian tube or primary peritoneal cancer)
  • Male breast cancer
  • BRCA1/2 mutation identified in tumor profiling
  • In the absence of personal history, family history of the above

See the USPSTF and NCCN guidelines below for additional information about specific testing criteria.

Genetics & Inheritance

HBOC is caused by a mutation in the BRCA1 or BRCA2 gene. When functioning normally, these genes are thought to serve as “caretakers” of the genome, correcting sporadic DNA errors due to faulty cell division or environmental exposures. Individuals with a mutation in BRCA1 or BRCA2 accumulate more DNA damage that can lead to cancer.

HBOC is an autosomal dominant condition. First-degree relatives of a BRCA1 or BRCA2 mutation carrier have a 50% chance of also carrying the mutation. Men and women are equally likely to inherit, and pass on, a mutation.

Clinical Testing

BRCA1 and BRCA2 genetic testing detects most cases of HBOC. Sequencing identifies 88-90% of individuals with a detectable BRCA1 or BRCA2 mutation and deletion/duplication analysis 10-12%. Individuals with Ashkenazi Jewish ancestry are typically offered testing for three mutations in BRCA1 and BRCA2 that commonly occur in that population with reflex to full sequencing and deletion/duplication analysis if indicated.

Expanded testing using a multi-gene panel that includes other cancer predisposition genes may identify additional families with hereditary breast cancer. Early estimates suggest that up to 50% of people meeting criteria for testing of the BRCA1 and BRCA2 genes will have a mutation in a different gene.


Increased surveillance (clinical breast exam, mammogram, and MRI) and consideration of risk reducing interventions (such as chemoprevention and preventive mastectomy or oophorectomy) are recommended. See the NCCN guidelines below. 

Other Genes that Contribute to Breast and Ovarian Cancer

There are other hereditary cancer syndromes that increase the risk for breast cancer, such as Cowden syndrome and Li-Fraumeni syndrome. The presentation of these syndromes in a family may overlap with that of HBOC, but can sometimes be distinguished based on characteristic features, such as physical exam findings. In addition, a number of common genetic susceptibility variants are thought to increase breast cancer risk to a lesser extent than BRCA1 and BRCA2. There are likely other genes that contribute to breast and ovarian cancer which have not yet been identified. See GeneReviews for more information about the genetic differential diagnosis for HBOC.

Select Guidelines & Resources


GeneReviews (2016): BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.

American Society of Clinical Oncology (2014): Hereditary Breast and Ovarian Cancer.

National Cancer Institute (2015): Genetics of Breast and Gynecologic Cancers PDQ – High-Penetrance Breast and/or Gynecologic Cancer Susceptibility Genes.


National Comprehensive Cancer Network (2017): Genetic/Familial High Risk Assessment: Breast and Ovarian (Free registration required for access).

U.S. Preventive Services Task Force (2013): Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women.

American College of Medical Genetics & National Society of Genetic Counselors (2014): Referral indications for cancer predisposition assessment.

American College of Obstetricians & Gynecologists (2009): Practice Bulletin #103:  Hereditary Breast and Ovarian Cancer Syndrome.

American College of Obstetricians and Gynecologists (2015): Committee Opinion #634: Hereditary Cancer Syndromes and Risk Assessment.

American Society of Clinical Oncology (2010): Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

American Society of Clinical Oncology & Society of Surgical Oncology (2006): ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes.

National Society of Genetic Counselors (2013): Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer.

National Society of Genetic Counselors (2012): Essential Elements of Genetic Cancer Risk Assessment, Counseling, and Testing: Updated Recommendations of the National Society of Genetic Counselors.