Third Trimester Estrogens and Maternal Breast Cancer: Prospective Evidence
Full-term pregnancy is associated both with a transient increase and life-time decrease in maternal breast cancer risk. Estrone (E1), estradiol (E2) and estriol (E3) are estrogens found in high concentrations during the third trimester. E1 and E2 metabolism produces carcinogenic intermediaries, while E3 metabolism does not.
We tested the hypothesis that higher estriol (E3) in pregnancy is protective, while higher estrone (E1) + estradiol (E2) increases risk.
Prospective case-cohort study (N=620; 204 breast cancer cases) nested in a 38-year follow-up of 15,528 pregnant women in the Child Health and Development Studies. We measured E1, E2 and E3 in archived third trimester pregnancy serum and estimated their association with breast cancer risk.
Northern California Kaiser Foundation Health plan members receiving obstetric care from 1959-1967.
Main Outcome Measure
Maternal breast cancer diagnosed through 1997. Results Overall, a doubling of E1+E2 was associated with greater risk (Hazard Ratio(HR)=1.7, 95% Confidence Interval(CI)=1.2-2.4). In contrast, doubling of E3 or the ratio of E3 to E1+E2 was associated with protection (HR=0.7, 95%CI=0.5-1.0 and HR=0.6, 95%CI=0.4-0.8 respectively). Associations were stronger for breast cancer diagnosed 2-15 years after delivery compared to 16-38 years (pinteraction=.0002), for gravidas age 27 at delivery versus age 27 (pinteraction =.01) and for primiparas versus multiparas (pinteraction =.02).
Relatively high third trimester E3 may protect parous women from breast cancer, while E1 and E2 may enhance risk. If findings are confirmed in other populations and supported experimentally, third trimester pregnancy estrogens could help explain how parity impacts breast cancer.