Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas

BACKGROUND. BRCA1 is a tumor suppressor gene that is responsible for heredi tary breast and ovarian carcinoma syndrome. The primary objective of the cu rrent study was to investigate the influence of BRCA1 expression on the pro gnoses of sporadic breast carcinomas. METHODS. A cohort of 175 Japanese women with invasive breast carcinoma who had no family history in first-degree relatives was studied. Expression of BRCA1 was determined by an immunohistochemical procedure in which the MS110 monoclonal antibody was used. Kaplan-Meier and Cox proportional regression survival analyses were used to compare negative and positive BRCA1 patient s. RESULTS. One hundred fifteen (65.7%) of the 175 specimens showed positive B RCA1 staining (> 10% cells were immunoreactive). During a median follow-up of 4.4 years, negative BRCA1 patients had worse disease free survival than positive BRCA1 patients (35% vs. 7%, respectively; P < 0.0001). BRCA1 expre ssion was significantly inversely correlated with histologic grade (P < 0.0 001) but not with lymph node status or other conventional prognostic marker s. In multivariate analysis using the Cox regression model, positive BRCA1 emerged as an independent prognostic indicator for disease free survival. CONCLUSIONS. The results of this study suggest that BRCA1 may be a valuable marker for identifying women with sporadic breast carcinoma at high risk o f developing recurrence, and who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy. Cancer 2001;9 2:54-60. (C) 2001 American Cancer Society.