BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast 
cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at 
young ages. In this study, the authors assessed age at diagnosis in 2 
generations of families with known mutations to investigate for earlier onset in 
subsequent generations.
METHODS: Of the 132 BRCA-positive women with breast cancer who participated in a 
high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 
106 women could be paired with a family member in the previous generation (Gen 
1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian 
cancer). Age at diagnosis, location of the mutation, and year of birth were 
recorded. A previously published parametric anticipation model was applied in 
these genetically predisposed families.
RESULTS: The median age of cancer diagnosis was 42 years (range, 28-55 years) in 
Gen 2 and 48 years (range, 30-72 years) in Gen 1 (P < .001). [corrected]. In the 
parametric model, the estimated change in the expected age at onset for the 
entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages 
at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, 
maternal inheritance, paternal inheritance, breast cancer only, and breast 
cancer-identified and ovarian cancer-identified families.
CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be 
diagnosed at an earlier age in later generations. The authors concluded that 
patients who are younger at the onset of BRCA-related cancers should continue to 
be tracked to offer appropriate screening modalities at appropriate ages.