Loss of heterozygosity in bilateral breast cancer

Women who develop bilateral breast cancer at an early age are likely to har bour germline mutations in breast cancer susceptibility genes. The aim of t his study was to test for concordant genetic changes in left and right brea st cancer of young women (age < 50) with bilateral breast cancer that may s uggest an inherited breast cancer predisposition. Microsatellite markers we re used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent t o or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (At axia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concorda nt LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each oc casion. This may suggest a common mutational event. Four cases showed conco rdant loss of alleles in both left and right breast cancer at D17S791 (BRCA 1). BRCA1 mutations were identified in two of these cases where blood was a vailable. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant L OH was further demonstrated in seven cases for D11S1778 (ATM) and four case s for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that ger mline mutations in p53 are unlikely in such cases of bilateral breast cance r.