Anticipation in hereditary breast cancer

To determine whether familial breast cancer occurs at a younger age in successive generations, we reviewed the clinical records of 435 Ashkenazi women with breast cancer referred to our cancer genetic clinic. Ninety‐eight who reported a maternal history of breast cancer were selected for further investigation. All women were genotyped for founder BRCA1/2 mutations (185delAG, 5382insC and 6174delT). Mean age at dignosis was 55.35 ± 14.21 years in the maternal generation and 48.17 ± 9.32 years in the daughters (t = − 4.144; p < 0.001). Seventeen women carried a BRCA1 mutation and 12 the 6174delT mutation in BRCA2. Among carriers of the BRCA1 mutation, mean age at diagnosis in the mothers' generation (44 ± 10.18 years) did not differ from that recorded in the daughters (40.76 ± 76 years). Among BRCA2 mutation carriers and non‐carriers, the mean age at diagnosis in the daughters' generation (41.4 ± 7.2 and 50.7 ± 8.8 years, respectively) was younger than in the mothers (61.75 ± 14.1 and 57.08 ± 13.7 years, respectively) (t = − 4.29; p < 0.001 for BRCA2 carriers and t=−3.76; p < 0.001 for non‐BRCA1/2 carriers). Daughters who were carriers of BRCA1/2 mutations developed breast c