Associations of established breast cancer risk factors with urinary estrogens in postmenopausal women

Purpose: Circulating estrogens are an established risk factor for postmenopausal breast cancer (BCa). We describe the distribution of urinary estrogens, their metabolites, and relevant metabolic pathway ratios among healthy postmenopausal women and examine associations of several known BCa factors with these estrogen measures.

Methods: Eligible postmenopausal women (n = 167) had no history of hormone use (previous 6 months) and cancer/metabolic disorders and had a body mass index (BMI) ≤ 35 kg/m². Estrogens were quantified in spot urine samples with liquid chromatography-high-resolution mass spectrometry and corrected for creatinine. We assessed overall distributions of estrogens and associations of age, BMI, race/ethnicity, parity/age at first birth, age at menarche, alcohol, and smoking with log-transformed estrogen measures using multivariate regression.

Results: BMI was positively associated with estrone (β per unit = 0.04, 95% Confidence Interval [CI] 0.00; 0.07), combined parent estrogens (β = 0.04, 95% CI 0.01; 0.07), and E2:total estrogens (β = 0.04, 95% CI 0.02; 0.06), and inversely associated with 4-MeOE1 (β = - 0.17, 95% CI - 0.33; - 0.02), E3:parent estrogens (β = - 0.04, 95% CI - 0.07; - 0.00), and 16-pathway:parent (β = - 0.04, 95% CI - 0.07; - 0.01). Being African American vs. white was associated with higher levels of 4-MeOE1 (β = 3.41, 95% CI 0.74; 6.08), 17-epiE3 (β = 1.19, 95% CI 0.07; 2.31), 2-pathway:parent (β = 0.54, 95% CI 0.04; 1.04), and lower levels of E2:total estrogens (β = - 0.48, 95% CI - 0.83; - 0.13). Having < 7 alcohol drinks/week vs. none was associated with higher levels of 16-ketoE2 (β = 1.32, 95% CI 0.36; 2.27), 16-epiE3 (β = 1.02, 95% CI 0.24; 1.79), and 17-epiE3 (β = 0.55, 95% CI 0.02; 1.08). Smoking was positively associated with E3:parent (β = 0.29, 95% CI 0.01; 0.57), 16-pathway:parent (β = 0.25, 95% CI 0.01; 0.49), and inversely associated with estradiol (β = - 0.52, 95% CI - 0.93; - 0.10). As compared to nulliparous, parous women with age at first birth ≥ 25 years had lower levels of estrone, combined parent estrogens, 2-OHE1, and 2-OHE2.

Conclusion: Our findings suggest that BMI, race/ethnicity, and some reproductive and lifestyle factors may contribute to postmenopausal BCa through their effects on circulating estrogens.