Understanding the Genetic Causes of Male Breast Cancer

A misconception about breast cancer is that it only affects women. While this idea is common, it is also incorrect. Breast cancer can and does affect men, especially if there is an inherited predisposition to developing breast cancer. Research has identified several genes that increase anyone’s chance of developing breast cancer, regardless of their sex. Understanding inherited causes can help people and their families understand their cancer risk and make informed healthcare decisions. 

Key Genes Linked to Male Breast Cancer 

Below is a summary of the 6 most common genes that can cause male breast cancer.

BRCA2 

Lifetime male breast cancer risk: up to 7% by age 70 

BRCA2 is the most significant gene linked to hereditary male breast cancer. Males with BRCA2 mutations have a markedly increased risk compared to the general male population (whose risk is  about 0.1%). BRCA2 mutations also increase the risk for prostate, pancreatic, melanoma and other cancers. 

BRCA1 

Lifetime male breast cancer risk: up to 1% by age 70

Although BRCA1 is strongly associated with breast and ovarian cancer in people assigned female at birth, it is less commonly associated with male breast cancer compared to BRCA2. However, BRCA1 can still confer a modestly elevated risk. There are also risks for prostate cancer and pancreatic cancer. There is emerging evidence of an association with melanoma as well. 

PALB2 

Lifetime male breast cancer risk: up to 1% by age 70 

PALB2 works closely with BRCA2 in DNA repair. While its risk contribution is much smaller than BRCA2, studies indicate an increased risk of male breast cancer in PALB2 mutation carriers. 

CHEK2 

Lifetime male breast cancer risk: More research is needed, but there may be a small breast cancer risk (near 1%) 

CHEK2 mutations have been linked to a moderately increased risk of breast cancer in both sexes, though evidence in males is less robust than in females. There is emerging evidence that CHEK2 mutations can also cause prostate cancer. 

PTEN (Cowden syndrome) 

Lifetime male breast cancer risk: Evidence suggests an increased risk, but more research is needed. 

PTEN mutations cause Cowden syndrome, a condition predisposing individuals to multiple cancers, including breast, thyroid, and endometrial cancers. While male breast cancer risk is believed to be elevated, exact percentages are not well established. 

TP53 (Li-Fraumeni syndrome) 

Lifetime male breast cancer risk: More research is needed, but there may be an increased risk. 

TP53 mutations cause a syndrome called Li-Fraumeni syndrome. TP53 mutations dramatically increase the risk of various cancers at young ages, including breast cancer. Cases of male breast cancer have been reported, although they are rare. 

In Summary

While rare, male breast cancer has clear genetic drivers, with BRCA2 standing out as the most significant. Genetic counseling and testing can empower individuals and their families with knowledge to take proactive steps for their health. 

If you have a family history of breast cancer, prostate cancer, or related cancers, consider talking to a healthcare provider or a genetic counselor about whether genetic testing is right for you.

Visit HIS Breast Cancer for information on how to perform a self breast exam to help with earlier detection.