Prognosis in BRCA1, BRCA2 associated breast cancer (BC): a prospective Breast Cancer Family Registry (BCFR) international population-based cohort study.

Abstract

Abstract Abstract #2072 Hereditary BC occurs at a younger age and is associated with more adverse tumor-related features than sporadic breast cancer (BC) (defined here as BC in those with no 1st or 2nd degree family history of breast or ovarian cancer). Using pre-specified criteria, we assembled a population-based cohort of newly diagnosed BC at 3 centers: Ontario, Canada (1996-98), San Francisco Bay area, USA (1995-2000), Melbourne/Sydney, Australia (1991-1998). Medical information was obtained from medical records; women were followed prospectively for recurrence, new cancers and death. Pathology data were obtained from central review or pathology reports. BRCA1 and BRCA2 mutation testing was performed on 77% and 70% of cases, respectively (sporadic BC cases were not tested at 2 centers). Hereditary and sporadic BC cases were compared using Cox proportional hazards (stratified by center). 3215 eligible cases were enrolled in the BCFR, with a mean age at diagnosis of 46.9 years. Median follow-up was 7.61 years; 565 women had distant recurrences and 547 died. There were 92 cases with BRCA1 and 72 with BRCA2 mutations; 1549 (48.2%) had sporadic BC; the remainder had familial BC as defined above. BRCA1 mutations were associated with young age, estrogen and progesterone receptor (ER and PgR) negativity and high grade; BRCA2 mutations were associated with node positivity and high grade. Distant disease-free survival (DDFS) and overall survival (OS) did not differ significantly between BRCA1 carriers and sporadic cases in univariate or multivariate analyses. DDFS and OS were worse in BRCA2 carriers than in sporadic cases (HR 1.6, p=0.04 and HR 1.8, p=0.01, respectively) in univariate analyses but not in multivariate analyses (DDFS HR 1.0, p=0.98; OS HR 1.13, p=0.61). The small group of BRCA2 carriers who did not receive adjuvant chemotherapy had a significantly worse OS (multivariate HR 3.63, p = 0.005). Furthermore, BRCA2 carriers who received adjuvant tamoxifen had significantly worse OS than women with sporadic BC (HR=2.0, p=0.03). We conclude that BRCA1 and BRCA2 mutations do not independently impact DDFS or OS. Significantly worse outcomes were seen in BRCA2 carrier subgroups defined by adjuvant treatment; this requires further investigation and may have implications for clinical practice. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2072.