Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case–control study in the Northern Sweden Maternity Cohort

Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case–control study in the Northern Sweden Maternity Cohort

Breast Cancer Research, July 2017

28720108

Renée T. Fortner, Eglé Tolockiene, Helena Schock, Husam Oda, Hans-Åke Lakso, Göran Hallmans, Rudolf Kaaks, Paolo Toniolo, Anne Zeleniuch-Jacquotte, Kjell Grankvist, Eva Lundin

Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones. We conducted a nested case-control study in the Northern Sweden Maternity Cohort (1975-2007). Eligible women had provided a blood sample in the first 20 weeks of gestation during a primiparous pregnancy leading to a term delivery. The current study includes 223 cases and 417 matched controls (matching factors: age at and date of blood collection). Estrogen receptor (ER) and progesterone receptor (PR) status was available for all cases; androgen receptor (AR) data were available for 41% of cases (n = 92). Sex steroids were quantified by high-performance liquid chromatography tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals were estimated using conditional logistic regression. Higher concentrations of circulating progesterone in early pregnancy were inversely associated with ER+/PR+ breast cancer risk (ORlog2: 0.64 (0.41-1.00)). Higher testosterone was positively associated with ER+/PR+ disease risk (ORlog2: 1.57 (1.13-2.18)). Early pregnancy estrogens were not associated with risk, except for relatively high estradiol in the context of low progesterone (split at median, relative to low concentrations of both; OR: 1.87 (1.11-3.16)). None of the investigated hormones were associated with ER-/PR- disease, or with AR+ or AR+/ER+/PR+ disease. Consistent with experimental models, high progesterone in early pregnancy was associated with lower risk of ER+/PR+ breast cancer in the mother. High circulating testosterone in early pregnancy, which likely reflects nonpregnant premenopausal exposure, was associated with higher risk of ER+/PR+ disease.