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 cancer, pancreatic cancer, 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, and a second primary tumor in a different tissue. 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. An estimated 1 in 333-500 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 (see Genetic Testing and Referral Criteria, below).

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.

While rare, individuals with BRCA2 mutations should be aware that if they have a child with another person who is also a BRCA2 mutation carrier, the child has a 25% chance of having Fanconi Anemia, characterized by bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain hematological cancers. Recently, there have been a few case reports of Fanconi-like conditions in individuals who carry two BRCA1 mutations.

Clinical Testing

Genetic 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 may be 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 risk. A significant number of people meeting criteria for testing of the BRCA1 and BRCA2 genes have a mutation in a different gene.

Genetic Testing and Referral Criteria

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
  • Ovarian (including Fallopian tube or primary peritoneal) cancer
  • Male breast cancer
  • Pancreatic cancer
  • Prostate cancer (metastatic, intraductal/cribiform histology, or high or very high grade)
  • Breast cancer diagnosed ≤ 45 y
  • Breast cancer diagnosed > 45 y with family history of related cancers
  • Triple negative breast cancer diagnosed at any age
  • Two primary tumors in the breast
  • Ashkenazi Jewish ancestry and breast cancer at any age
  • 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 testing criteria.


Increased surveillance (clinical breast exam, mammogram, and MRI) and consideration of risk reducing interventions (such as chemoprevention and preventive mastectomy or oophorectomy) are recommended, as well as consideration of targeted therapeutics for affected patients. 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, moderate risk genes and 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.

Select Guidelines & Resources


American Society of Clinical Oncology (2020): Hereditary Breast and Ovarian Cancer.

National Cancer Institute (2021): Genetics of Breast and Gynecologic Cancers PDQ.

National Society of Genetic Counselors (2021): Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer Syndromes.


National Comprehensive Cancer Network (v.1.2022): Genetic/Familial High Risk Assessment: Breast, Ovarian and Pancreatic (free registration required for access).

U.S. Preventive Services Task Force (2019): BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing.

American College of Obstetricians & Gynecologists (2017): Practice Bulletin #182:  Hereditary Breast and Ovarian Cancer Syndrome.

American College of Obstetricians and Gynecologists (2019): Committee Opinion #793: Hereditary Cancer Syndromes and Risk Assessment.

American Society of Clinical Oncology (2020): Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline.

American Society of Clinical Oncology (2015): Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

Updated December 2021