Baseline E(2) levels are higher in BRCA2 mutation carriers: a potential target for prevention?

Abstract

Purpose: 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.

Methods: We measured baseline (menstrual cycle day 2-3) E(2) levels of 96 women with breast cancer who underwent BRCA testing.

Results: 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 ± 12.6 pg/ml in BRCA2 mutation carriers, BRCA1 mutation carriers, and non-carriers, respectively, p value = 0.03). Women with BRCA2 mutations had 3.1 times as great risk for high basal E(2) level (>48 pg/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 ± 4.9 years, p = 0.04).

Conclusions: 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.

Fig. 1. Comparison of basal serum estradiol (E₂) levels by BRCA mutation status

The upper and lower T bars denote maximum and minimum values, respectively. The lines inside the plot boxes denote median values and dots denote mean values. The numbers above the upper T bars denotes “mean baseline serum E₂ levels ± standard deviation” in each group. ^ap<0.017 compared to BRCA(−) group analyzed by multiple comparisons with a Bonferroni adjustment