Tikk, KajaSookthai, DisornFortner, Renée TJohnson, TheronRinaldi, SabinaRomieu, IsabelleTjønneland, AnneOlsen, AnjaOvervad, KimClavel-Chapelon, FrançoiseBaglietto, LauraBoeing, HeinerTrichopoulou, AntoniaLagiou, PagonaTrichopoulos, DimitriosMasala, GiovannaKrogh, VittorioTumino, RosarioRicceri, FulvioMattiello, AmaliaAgudo, AntonioMenéndez, VirginiaSanchez-Perez, Maria-JoseAmiano, PilarChirlaque, Maria-DoloresBarricarte, AurelioBueno-de-Mesquita, HBasMonninkhof, Evelyn MOnland-Moret, N CharlotteAndresson, AnneSund, MalinWeiderpass, ElisabeteKhaw, Kay-TeeKey, Timothy JTravis, Ruth CMerritt, Melissa ARiboli, ElioDossus, LaureKaaks, Rudolf2015-09-102015-09-102015-03-31Tikk K, Sookthai D, Fortner RT, Johnson T, Rinaldi S, Romieu I, et al. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study. Breast Cancer Res. 2015; 17(1): 491465-5411http://hdl.handle.net/10668/1982JOURNAL ARTICLE;INTRODUCTION The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. METHODS We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. RESULTS We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95%CI 1.04-1.76), Ptrend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to ≥4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07). CONCLUSIONS Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.spaNeoplasias de la MamaCarcinoma in SituEstudios de Casos y ControlesProlactinaRiesgoMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in SituMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control StudiesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Gonadotropins::Gonadotropins, Pituitary::ProlactinMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Riskresearch article25887963open access10.1186/s13058-015-0563-61465-542X