Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations

Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations.

We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient.

Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months).

Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.