Summary To confirm several recent studies pointing to loss of heterozygosity (LOH) at BRCA2 as a prognostic factor in sporadic breast cancer, we examined this genetic alteration in a large series of human primary breast tumours for which long-term patient outcomes were known. LOH at BRCA2 correlated only with low oestrogen and progesterone receptor content. Univariate analysis of metastasis-free survival and overall survival (log-rank test) showed no link with BRCA2 status (P = 0.34, P = 0.29 respectively). LOH at BRCA2 does not therefore appear to be a major prognostic marker in sporadic breast cancer.Keywords: BRCA2; loss of heterozygosity; prognostic value; breast cancer Breast cancer, one of the most common life-threatening diseases in women, occurs in hereditary and sporadic forms. The two major breast cancer susceptibility genes, BRCAI and BRCA2, were recently isolated (Miki et al, 1994;Wooster et al, 1995;Couch et al, 1996). Both are considered to be tumour-suppressor genes and are thought to be inactivated by a 'two-hit' mechanism originally proposed by Knudson to explain the tumorigenesis of retinoblastoma. In hereditary cancer, the first hit would be a germline mutation in a specific cancer gene, whereas in sporadic cancer the first hit would be a somatic mutation or another inactivating molecular event. The second hit would be a loss of the second gene copy in the somatic cell, in both hereditary and sporadic forms. A number of germline mutations in the BRCAJ and BRCA2 genes have been identified in families prone to breast cancer (Shattuck-Eidens et al, 1995;Couch et al, 1996. In sporadic forms, somatic BRCA2 mutations, like somatic mutations in the BRCAJ gene, are rare Miki et al, 1996;Teng et al, 1996). However, aberrant subcellular location (Chen et al, 1995) and reduced expression of BRCAJ (Thompson et al, 1995), together with high frequencies of loss of heterozygosity (LOH) on 17ql2-q21 and 13ql2-ql3 (sites of BRCAI and BRCA2) (Bieche and Lidereau, 1995), point to a significant role of these two genes in the tumorigenesis of sporadic breast cancer, but through a mechanism other than structural mutation. LOH on 13ql2-ql3 occurs in 30-60% of somatic breast tumours (Cleton-Jansen et al, 1995;Kerangueven et al, 1995;Beckmann et al, 1996;Hamann et al, 1996;Kelsell et al, 1996). These LOH studies identified a consensus region of deletion involving BRCA2 and excluding the RB 1 locus. Several studies have pointed to a link between BRCA2 inactivation (mutation and/or LOH) and Scarff, Bloom and Richardson (SBR) histopathological grade 3, in both hereditary and sporadic forms of breast cancer, suggesting the involvement of