Bilateral breast cancer and local relapse: A hospital-based study of the prevalence of BRCA 1 and BRCA 2 gene mutations

Background: Mutations of the BRCA 1/BRCA 2 genes strongly predispose toward s the development of contralateral breast cancer. We therefore investigated a hospital-based series of patients with bilateral breast cancer and a com parison group of patients with unilateral breast cancer, pairwise matched b y age and family history, for mutations of the BRCA 1/BRCA 2 genes. Patients and Methods: Between 1995 and 2000 genomic DNA from blood samples of 75 patients with bilateral breast cancer, who received postoperative rad iotherapy, was analyzed for mutations of all coding regions and flanking in tron sequences of the BRCA 1/BRCA 2 genes by single strand conformation pol ymorphism analysis (SSCP) and sequencing of aberrant findings. The results were compared to 75 unilateral breast cancer patients who were screened for common mutations in the BRCA 1 and BRCA 2 genes. Treatment results of pati ents with bilateral disease were analyzed with regard to a possible carrier ship of a BRCA 1/BRCA 2 gene mutation. Results: Five distinct frameshift deletions (one in BRCA 1, four in BRCA 2) were identified in six patients with bilateral breast cancer. Three of six carriers developed Local relapse, whereas this was the case in only nine o f 69 non-carriers, After radiotherapy Local relapse occurred in five patien ts (five of 126 irradiated breasts or chest walls). Three of these patients (60%) were carriers of a pathogenic BRCA 1/BRCA 2 mutation. In the compari son group of patients with unilateral breast cancer three pathogenic BRCA 1 mutations were identified. Conclusions: We failed to confirm an increased prevalence of BRCA 1/BRCA 2 mutations in our hospital-based series of patients with bilateral breast ca ncer. However, local relapse, especially when occurring after radiotherapy, may be predictive for an underlying pathogenic BRCA 1 and BRCA 2 gene muta tion in patients with bilateral breast cancer.