What gene is most strongly associated with male breast cancer?

Male Breast Cancer is Most Strongly Associated with BRCA2 Gene

Male breast cancer is most strongly associated with the BRCA2 gene, with a lifetime risk of up to 8% in carriers, compared to only 1.2% for BRCA1 carriers. 1

Genetic Associations with Male Breast Cancer

BRCA2 - Primary Association

• BRCA2 mutations confer the highest risk for male breast cancer:
  • Lifetime risk of 6-8% by age 70 years 1, 2
  • This is substantially higher than the general population risk of ~0.1% 1
  • BRCA2 is the main male breast cancer susceptibility gene, accounting for approximately 10% of all male breast cancer cases 1, 3

BRCA1 - Secondary Association

• BRCA1 mutations are associated with male breast cancer but at significantly lower rates:
  • Lifetime risk of only 1.2% by age 70 years 1, 2
  • Only 0-4% of male breast cancer cases have BRCA1 mutations 1

Other Genetic Associations

• Other genes associated with male breast cancer include:
  • PALB2 - emerging evidence suggests increased risk 1, 4, 3
  • CHEK2 - confers moderate risk 1, 3
  • PTEN - less common but appears to confer elevated risk 1

Risk Modifiers in Male Breast Cancer

• Risk can be substantially increased in BRCA2 carriers with:
  • Gynaecomastia (RR 9.8) 1
  • Klinefelter syndrome (RR 24.7) 1
  • Family history of breast cancer 1, 5

Clinical Implications

• All male breast cancer patients should be offered genetic counseling and testing for germline mutations 1
• Annual mammography or ultrasound screening should be considered in male BRCA2 carriers with additional high-risk features from age 50 or 10 years before the earliest male breast cancer in the family 1
• Male BRCA2 carriers should be encouraged to be aware of physical changes in the breast and seek medical attention accordingly 1

Pathological Features

• BRCA2-associated male breast cancers tend to be of higher grade than sporadic male breast cancers 6
• BRCA2 male breast cancers are more likely to be estrogen receptor-positive and progesterone receptor-positive compared to BRCA2 female breast cancers 6

In conclusion, while multiple genes can contribute to male breast cancer risk, the BRCA2 gene shows the strongest and most consistent association, with substantially higher risk than BRCA1 or other breast cancer susceptibility genes.