Baseline E2 levels are higher in BRCA2 mutation carriers: a potential target for prevention?

Abstract

BRCA gene mutations and elevated serum estradiol (E(2)) are well-known risk factors for breast cancer. The aim of this study was to investigate the association between BRCA gene mutations and serum E(2) level. We measured baseline (menstrual cycle day 2-3) E(2) levels of 96 women with breast cancer who underwent BRCA testing. The mean age, parity, and age at menarche did not differ between women with and without BRCA1/2 mutations. Basal serum E(2) level was significantly higher in women with BRCA2 mutations compared to women with BRCA1 mutations or without BRCA mutations (71.7±41.6 vs. 45.5±20.7 vs. 38.5±12.6pg/ml in BRCA2 mutation carriers, BRCA1 mutation carriers, and non-carriers, respectively, p value=0.03). Women with BRCA2 mutations had 3.1times as great risk for high basal E(2) level (>48pg/ml) as women without BRCA mutations after adjusting for age and BMI (95% confidence interval: 1.3, 7.6). BRCA mutation carriers with high serum E(2) level were significantly younger than the carriers with low serum E(2) level (31.4±3.1 vs. 34.7±4.9years, p=0.04). In this pilot study, we found an association between high basal serum E(2) levels and BRCA2 mutations. Our results suggest that increased production of E(2) may have a role in the pathogenesis of BRCA2-mutation-related breast cancer.