Incidence of Hereditary Breast Cancer with BRCA1 and BRCA2 Gene Mutations

Prevalence of BRCA Mutations

The American College of Medical Genetics and Genomics estimates that familial susceptibility accounts for approximately 25% of all breast cancer cases 1
The prevalence of BRCA mutation carriers in the general population is estimated at between 1/800 and 1/1000 1
BRCA1 and BRCA2 mutation frequencies in breast cancer patients unselected for family history or age at onset are generally low: <1-7% for BRCA1 and 1-3% for BRCA2 1, 3
Higher prevalence is associated with family history of breast or ovarian cancer, young age at onset, male breast cancer, or multiple tumors 1
In the Ashkenazi Jewish population, the prevalence of specific BRCA mutations is significantly higher at approximately 1/50 4

BRCA1 mutation carriers have a 65-80% lifetime risk of developing breast cancer 1, 2
BRCA1 mutation carriers have a 37-62% lifetime risk of developing ovarian cancer 1, 5
Breast cancers in BRCA1 mutation carriers tend to be of the basal-like phenotype, high histologic grade, and often triple-negative 2

BRCA2 mutation carriers have a 45-85% lifetime risk of developing breast cancer 1, 2
BRCA2 mutation carriers have a 11-23% lifetime risk of developing ovarian cancer 1, 5
BRCA2 mutation carriers have a 5-10% lifetime risk of male breast cancer 2, 6
BRCA2-related tumors more closely resemble sporadic tumors 2

The National Comprehensive Cancer Network recommends genetic testing referral for individuals with three or more breast and/or ovarian cancer cases with at least one diagnosed before age 50; two breast cancer cases diagnosed before age 40; male breast cancer with early-onset female breast cancer; and breast and ovarian cancer in the same patient 1, 3
Genetic testing should be performed after genetic counseling and informed consent 1
Surveillance for BRCA carriers includes monthly self-examinations, clinical breast examinations once or twice a year, and yearly mammograms and MRI starting at age 25-30 3

The American Cancer Society notes that despite identification of multiple susceptibility genes, more than 70% of familial breast cancer cases remain unexplained genetically 8
A negative BRCA1/2 test does not rule out hereditary breast cancer risk if family history remains suggestive 8
Mutations in other high-penetrance genes (TP53, PTEN, CDH1, STK11) also contribute to hereditary breast cancer but are rarer than BRCA1/2 mutations 2, 8