What are the screening and preventive measures for male breast cancer in individuals with a family history of breast cancer or known BRCA1 (Breast Cancer Gene 1) or BRCA2 (Breast Cancer Gene 2) mutations?

Male Breast Cancer and BRCA1/2: Screening and Prevention

All male patients diagnosed with breast cancer should be offered genetic counseling and testing for germline mutations, as approximately 20% carry an identifiable inherited risk factor, with BRCA2 mutations being particularly common (4-16% of cases). 1

Association Between BRCA Mutations and Male Breast Cancer

Male breast cancer shows a strong but differential association with BRCA mutations compared to female breast cancer:

• BRCA2 carriers have a cumulative breast cancer risk of 6.8% by age 70, representing a substantially elevated risk compared to the general male population (approximately 0.1% lifetime risk) 1, 2
• BRCA1 carriers have a cumulative breast cancer risk of 1.2% by age 70, which is lower than BRCA2 but still significantly elevated 1, 2
• Among male breast cancer patients, 0-4% carry BRCA1 mutations and 4-16% carry BRCA2 mutations 1
• BRCA2 is overrepresented in male breast cancer (41.7%) compared to female breast cancer (8.3%), while BRCA1 is underrepresented (5.0% vs 14.4% in females) 3

Screening Recommendations for Men with BRCA Mutations

Clinical Breast Examination

• Annual clinical breast examination starting at age 35 years for men with BRCA1/2 mutations 4

Mammography Screening

• Contralateral annual mammogram may be offered to men with a history of breast cancer and a genetic predisposing mutation 1
• Annual mammography or ultrasound screening should be considered in male BRCA2 carriers with additional high-risk features such as gynecomastia or Klinefelter syndrome, starting at age 50 or 10 years before the earliest male breast cancer in the family 1, 4
• The cancer detection rate for mammography in high-risk men is higher than that seen in both average-risk and high-risk women undergoing breast screening 4

Breast MRI

• Breast MRI is not recommended routinely in men with a history of breast cancer, based on the relatively small amount of breast tissue in most men, lack of survival benefit data, and potential for false positives 1

Breast Self-Awareness

• Male BRCA2 carriers should be encouraged to be aware of physical changes in the breast and seek medical attention accordingly 1

Screening for Other Cancers in Male BRCA Carriers

Prostate Cancer Screening

• Annual PSA screening should be offered to male BRCA2 carriers from age 40 years, as BRCA2 carriers have higher incidence of prostate cancer, are diagnosed significantly younger, and present with more aggressive disease 1
• Annual PSA screening may also be considered for male ATM carriers from age 40 years 1

Pancreatic Cancer Screening

• Screening with annual contrast-enhanced MRI and/or endoscopic ultrasound from age 50 (or 5-10 years younger than the affected relative) may be considered in BRCA1, BRCA2, or PALB2 carriers with at least one first- or second-degree relative with pancreatic cancer 1

Genetic Testing Indications

All male patients with breast cancer should be offered genetic counseling and testing, regardless of family history, as male breast cancer itself is a criterion for genetic testing 1, 5

Benefits of Genetic Testing Identification

1. Influences screening recommendations for other types of cancer (prostate, pancreatic) 1
2. Enables cascade testing of family members for inherited risk factors 1
3. Identifies treatment opportunities for patients with metastatic breast cancer (e.g., PARP inhibitors) 1

Testing Should Include

• BRCA1 and BRCA2 genes 1
• Other genes such as CHEK2, PALB2, and PTEN, which also confer elevated breast cancer risk in men 1, 6

Family History Assessment

Men with the following family history features should be considered for genetic counseling:

• Two or more close relatives with breast or ovarian cancer 1
• Breast cancer occurring before age 50 years in a close relative 1
• Family history of both breast and ovarian cancer 1
• One or more relatives with two cancers (breast and ovarian or two independent breast cancers) 1
• Other male relatives with breast cancer 1

Important Clinical Considerations

Risk Factors Beyond BRCA

• Gynecomastia increases male breast cancer risk (RR 9.8) 1
• Klinefelter syndrome substantially increases risk (RR 24.7) 1
• Men with these conditions warrant enhanced surveillance even without identified BRCA mutations 1

Post-Treatment Surveillance

• Ipsilateral annual mammogram should be offered to men with a history of breast cancer treated with lumpectomy, if technically feasible, regardless of genetic predisposition 1

Evidence Quality Note

The evidence for male breast cancer screening is of low quality, as there are no clinical trials demonstrating mortality benefit from screening in this population 1. However, given the substantially elevated risk in BRCA2 carriers and the higher cancer detection rate in high-risk men, screening is recommended based on expert consensus and extrapolation from female data 4.