Mutations of the BRCA1 and BRCA2 genes in patients with bilateral breast cancer

Mutations of the BRCA1 or BRCA2 genes have been shown to strongly predispos e towards the development of contralateral breast cancer in patients from l arge multi-case families. In order to test the hypothesis that BRCA1 and BR CA2 mutations are more frequent in patients with bilateral breast cancer, w e have investigated a hospital-based series of 75 consecutive patients with bilateral breast cancer and a comparison group of 75 patients with unilate ral breast cancer, pairwise matched by age and family history, for mutation s in the BRCA1 and BRCA2 genes. Five frameshift deletions (517delGT in BRCA 1; 4772delA, 5946delCT, 6174delT and 8138del5 in BRCA2) were identified in patients with bilateral disease. No further mutations, apart from polymorph isms and 3 rare unclassified variants, were found after scanning the whole BRCA1 and BRCA2 coding sequence. Three pathogenic BRCA1 mutations (Cys61 Gl y, 3814de15, 5382insC) were identified in the group of patients with unilat eral breast cancer. The frequencies of common BRCA1 and BRCA2 missense vari ants were not different between the 2 groups. In summary, we did not find a significantly increased prevalence of BRCA1 and BRCA2 mutations in a hospi tal-based cohort of German patients with bilateral breast cancer. We conclu de that bilaterality of breast cancer on its own is not strongly associated with BRCA1 and BRCA2 mutations when adjusted for age and family history. T he high frequency of bilateral disease in multi-case breast cancer families may be due to a familial aggregation of additional susceptibility factors modifying the penetrance of BRCA1 and BRCA2 mutations. (C) 2001 Cancer Rese arch Campaign.