What is the significance of BRCA1 (Breast Cancer Gene 1) and BRCA2 (Breast Cancer Gene 2) in breast cancer?

From the Guidelines

Women with BRCA1 or BRCA2 mutations should undergo enhanced surveillance, including annual mammography and magnetic resonance imaging (MRI), starting at age 25, as well as risk-reducing salpingo-oophorectomy (RRSO) by age 35-40, to reduce their risk of breast and ovarian cancer. This is based on the most recent and highest quality evidence, which suggests that these interventions can significantly reduce the risk of cancer in individuals with BRCA mutations 1.

Key Points

• BRCA1 and BRCA2 mutations increase the risk of breast and ovarian cancer, with lifetime risks of 55-72% and 39-44% for BRCA1, and 45-69% and 11-17% for BRCA2, respectively.
• Testing for BRCA mutations is recommended for individuals with a strong family history of breast, ovarian, pancreatic, or prostate cancer, especially at young ages.
• Management options for individuals with BRCA mutations include enhanced surveillance, risk-reducing medications, and preventive surgeries.
• Genetic counseling is essential before and after testing to help individuals understand their results and make informed decisions about risk management.
• The use of tamoxifen and other risk-reducing medications may also be considered, although the evidence for their effectiveness in individuals with BRCA mutations is limited 1.

Surveillance and Prevention

• Annual mammography and MRI should be started at age 25 for women with BRCA1 or BRCA2 mutations.
• RRSO should be performed by age 35-40, or earlier if childbearing is complete or there is a family history of ovarian cancer.
• Prophylactic mastectomy may also be considered, although the decision to undergo this procedure should be made on an individual basis.

Risk-Reducing Medications

• Tamoxifen may be considered for women with BRCA1 or BRCA2 mutations who have not undergone prophylactic oophorectomy before menopause, although the evidence for its effectiveness is limited 1.
• Other risk-reducing medications, such as aromatase inhibitors, may also be considered, although more research is needed to determine their effectiveness in individuals with BRCA mutations.

From the Research

BRCA1 and BRCA2 Mutation Carriers

• Women with BRCA1 or BRCA2 mutations are at high risk for the development of breast cancer 2
• Current recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every 6 months 3

Screening Modalities

• Magnetic resonance imaging (MRI) is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone in BRCA1 and BRCA2 mutation carriers 3, 4
• The sensitivity and specificity of MRI were 77% and 95.4%, respectively, compared to 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE 3
• Combining all four screening modalities (MRI, mammography, ultrasound, and CBE) had a sensitivity of 95% compared to 45% for mammography and CBE combined 3

Risk Management

• Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are recommended for BRCA1/2 mutation carriers to reduce mortality 5
• Nipple-areolar sparing mastectomy (NSM) is now an option for BRCA1/2 mutation carriers 5
• Breast-conserving therapy (BCT) is an appropriate treatment option for BRCA1/2 mutation carriers with breast cancer, but mastectomy and contralateral risk-reducing mastectomy should be considered to reduce the risk of second primary breast cancer 5

Special Considerations

• Pregnant and breastfeeding women with BRCA mutations require special consideration for breast cancer screening due to hormonal shifts that may affect the sensitivity and specificity of screening modalities 6
• Transgender BRCA1 and BRCA2 mutation carriers also require special consideration for breast cancer screening 2