title: Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer.
abstract: Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (± 6 months) and date of sampling (± 3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed ≥ age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), p(interaction) 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. a.lukanova@dkfz.de
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Helja-Marja
authors.initials: HM
authors.lastname: Surcel
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.forename: Marjo
authors.initials: M
authors.lastname: Kaasila
authors.forename: Hans-Ake
authors.initials: HA
authors.lastname: Lakso
authors.forename: Helena
authors.initials: H
authors.lastname: Schock
authors.forename: Anika
authors.initials: A
authors.lastname: Husing
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Pentti
authors.initials: P
authors.lastname: Koskela
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.forename: Paolo
authors.initials: P
authors.lastname: Toniolo
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000209:etiology*; D016022:Case-Control Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D011247:Pregnancy / Q000097:blood*; D011374:Progesterone / Q000097:blood*; D011960:Receptors, Estrogen / Q000032:analysis; D012306:Risk
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D011374:Progesterone