Male Breast Cancer Risk in ATM Mutation Carriers
Male carriers of pathogenic ATM mutations have a modestly increased risk of breast cancer with an odds ratio of approximately 3.4, though the absolute lifetime risk remains low at less than 2%. 1
Quantified Risk Estimates
The evidence for male breast cancer risk in ATM mutation carriers is limited but consistent:
A recent study identified ATM pathogenic variants in 4 out of 340 BRCA1/2-negative male breast cancer cases, generating an odds ratio of 3.36 (95% CI 0.89-8.96, P=0.04). 1
An earlier Greek study found that approximately 2% of males with breast cancer harbor pathogenic variants in ATM. 1
Among 627,742 patients referred for multigene panel testing including 4,607 ATM heterozygotes, male breast cancer showed an odds ratio of 1.72 (95% CI 1.08-2.75). 2
Context and Comparison to Other Genes
The risk for male breast cancer in ATM carriers is substantially lower than in BRCA2 carriers:
Male BRCA2 carriers have a cumulative lifetime risk of 7-8% for breast cancer. 1
Male BRCA1 carriers have a cumulative lifetime risk of 1.2% for breast cancer. 1
In contrast, men without BRCA1/2 mutations have a baseline lifetime risk of approximately 0.1% (1 in 1,000). 1
Strength of Evidence
The evidence for increased male breast cancer risk in ATM carriers is characterized as "weak" by the most recent ACMG clinical practice resource (2025). 1 This reflects:
- Small absolute numbers of cases in published studies
- Wide confidence intervals that sometimes cross 1.0
- Limited prospective data
- Most evidence comes from case-control studies rather than prospective cohort studies
Clinical Implications
Annual mammography or ultrasound screening should be considered in male ATM carriers only if they have additional high-risk features such as gynecomastia or Klinefelter syndrome, starting from age 50 or 10 years before the earliest male breast cancer in the family. 1
Male ATM carriers should be encouraged to be aware of physical changes in the breast and seek medical attention for any breast masses, skin changes, or nipple discharge. 1
Important Caveats
The risk estimates are primarily derived from populations of European descent, and may not be generalizable to other ethnic groups. 1
Unlike female breast cancer risk in ATM carriers (which is well-established at approximately 2-fold increased risk), the male breast cancer association remains less certain due to the rarity of male breast cancer overall. 1
Routine screening mammography is not recommended for male ATM carriers without additional risk factors, as there is little evidence of efficacy. 1