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

• Main Authors: Fortner, Renée, Eglé Tolockiene, Schock, Helena, Oda, Husam, Hans-Åke Lakso, Hallmans, Göran, Kaaks, Rudolf, Toniolo, Paolo, Zeleniuch-Jacquotte, Anne, Grankvist, Kjell, Lundin, Eva
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: Figshare 2017
• Subjects: Medicine; Cell Biology; Genetics; FOS Biological sciences; Physiology; Biotechnology; 39999 Chemical Sciences not elsewhere classified; FOS Chemical sciences; Sociology; FOS Sociology; 69999 Biological Sciences not elsewhere classified; 19999 Mathematical Sciences not elsewhere classified; FOS Mathematics; Cancer; Northern Sweden
• Online Access: https://dx.doi.org/10.6084/m9.figshare.c.3830083.v1; https://figshare.com/collections/Early_pregnancy_sex_steroids_during_primiparous_pregnancies_and_maternal_breast_cancer_a_nested_case_control_study_in_the_Northern_Sweden_Maternity_Cohort/3830083/1

Abstract Background Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones. Methods 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. Results 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. Conclusions 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.