Hereditary Breast and Ovarian Cancer syndrome (HBOC)

Hereditary Breast and Ovarian Cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. In families with mutations in the BRCA1 or BRCA2 genes, typical characteristics include:

  • early-onset breast cancer (occurring before the age of 50 years),
  • ovarian, fallopian tube or primary peritoneal cancer
  • triple-negative breast cancer
  • bilateral breast cancer, or breast and ovarian cancer in the same individual
  • breast cancer in men
  • metastatic prostate cancer
  • multiple generations affected on the same side of the family
  • Ashkenazi Jewish ancestry (there are two mutations in BRCA1 and one mutation in BRCA2 that are common in this population, found in approximately 1 in 40 individuals)
  • in some families there may also be an increased incidence of melanoma and/or pancreatic cancer

Mutations in BRCA1 and BRCA2 are inherited in an autosomal dominant pattern, meaning that children of a mutation carrier each have a 50% risk to inherit the mutation and associated cancer risks. Notably, women and men both have the BRCA1 and BRCA2 genes and have the same chances to inherit and pass down mutations in these genes. Therefore, both sides of the family are important when assessing inherited risk. However, the associated cancers and lifetime risks are different between men and women.

Cancer type Risk in the general population Risk in BRCA1 mutation carriers Risk in BRCA2 mutation carriers
Female Breast 12% 60-80% 50-70%
Second Breast 1.5% per year Up to 20% within 5 years Up to 12% within 5 years
Ovarian 1-2% 34-44% 12-20%
Male Breast 0.10% Risk increased 7%
Prostate 16% Risk increased 20-30%
Pancreatic 0.9% 2-3% 3-5%
Melanoma 1-2% n/a 3-5%

 

Genetic testing for BRCA1 and BRCA2

Genetic testing for mutations in BRCA1 and BRCA2 has been available for many years, and the testing methods have changed and improved over time. There are several different ways to approach to testing in these genes, depending on the history and any prior testing that may have been done. Different approaches include:

  • Single site analysis: Testing specific to a known mutation in the family
  • Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable mutations in the genes. If past testing included full gene sequencing but not the rearrangement analysis, this additional testing can be ordered to evaluate for these types of mutations that would have been missed on older testing.
  • Founder mutation testing: Testing specific to the three common mutations found in the Ashkenazi Jewish population
  • Gene panels: Newer, more broadly based gene tests that would include not only the BRCA1 and BRCA2 genes, but other genes known or suspected to be associated with increased cancer risks    

Who should be offered testing for BRCA1 and BRCA2?

Other than someone’s personal history of cancer, another piece of information that we can use to help determine if someone is at a higher risk to have a mutation in the BRCA1 and BRCA2 genes is your family history. The National Comprehensive Cancer Network (NCCN) is a group of medical professionals that regularly meet to look over any updates in research studies and determine recommendations for who should be considered at a higher risk for one of these gene mutations, and thus should be offered genetic testing.

Some things in the family history (make sure to include yourself in your family history if you have been diagnosed with cancer) that may put someone at a higher risk for a BRCA1 or BRCA2 mutation are:

  • A family history of ovarian cancer
  • A family history of metastatic (cancer that has spread to other parts of the body) prostate cancer
  • A family history of breast cancer diagnosed before age 50
  • A family history of triple-negative (a specific type) breast cancer diagnosed before age 60
  • A family history of three or more relatives (on the same side of the family), that have had breast, pancreatic, or prostate cancer
  • Ashkenazi Jewish ancestry and a family history of breast, ovarian, pancreatic, or prostate cancer

These are some loose guidelines for who may be at an increased risk, but a medical professional, such as a genetic counselor, will be able to meet with you to further flush out your family history and help determine if you meet criteria for genetic testing.

Cancer Screening and Risk Management for BRCA1 and BRCA2

If you are tested and found to have a mutation in the BRCA1 or BRCA2 gene, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic. General recommendations are included here based on the updated guidelines of the (NCCN), but may be tailored to your specific medical and family history.  

Breast cancer screening for women with a BRCA1 or BRCA2 mutation includes:

  • Beginning at age 18: Breast self exam to facilitate awareness and familiarity with breast tissue
  • Ages 25-29: Clinical breast exam (every 6-12 months) and breast MRI (every 12 months)
  • Ages 30-75: Clinical breast exam (every 6-12 months), breast MRI (every 12 months), and mammogram (every 12 months)
  • Age 75+: Individualized management

Bilateral prophylactic (preventive) mastectomies or preventive medications are also available options for breast cancer risk reduction, and are a personal decision.  

Women at increased risk for ovarian cancer due to having a BRCA1 or BRCA2 mutation are encouraged to consider prophylactic (preventative) removal of the ovaries and fallopian tubes between age 35-40, or once they are finished having children. For women who do not elect preventive surgery, current ovarian cancer screening includes CA-125 blood levels and transvaginal ultrasound beginning at age 30-35, however this screening is not proven to be effective and is not recommended by many medical organizations.

For men with a BRCA1 or BRCA2 mutation, recommendations include regular breast self exams and annual clinical breast exams beginning at age 35. Men should also adhere to screening guidelines for prostate cancer beginning at age 45.

In families with a BRCA1 or BRCA2 mutation and a history of melanoma and/or pancreatic cancer, individualized screening may be offered based on the history, but no specific guidelines currently exist.  


Last updated on Dec 22nd, 2017