Plasma prolactin and postmenopausal breast cancer risk: a pooled analysis of four prospective cohort studies

Abstract

Background: Prolactin, a hormone produced by the pituitary gland, regulates breast development and may contribute to breast cancer etiology. However, most epidemiologic studies of prolactin and breast cancer have been restricted to single, often small, study samples with limited exploration of effect modification.

Methods: The Biomarkers in Breast Cancer Risk Prediction consortium includes 8,279 postmenopausal women sampled from four prospective cohort studies, of whom 3,441 were diagnosed with invasive breast cancer after enrollment. Prolactin concentrations were measured for all study participants on plasma samples collected when all women were postmenopausal and before any breast cancer diagnosis using ELISA assays. Pooled, unconditional logistic regression models, adjusted for confounders, estimated odd ratios (OR) for associations of prolactin and postmenopausal breast cancer risk overall and stratified by breast cancer risk factors.

Results: Higher plasma prolactin concentrations were positively associated with postmenopausal breast cancer risk (> 13.2 ng/mL vs. < 7.9 ng/mL, OR: 1.20, 95% CI: 1.06, 1.36; P-trend < 0.001). Although associations did not appear to vary by time since blood draw or most breast cancer risk factors, associations were primarily observed in current users of postmenopausal hormones at blood draw (> 13.2 ng/mL vs. < 7.9 ng/mL, current users, OR: 1.58, 95% CI: 1.27, 1.96, P-trend < 0.001; non-current users, OR: 1.08, 95% CI: 0.93, 1.27, P-trend = 0.11; P-heterogeneity = 0.06).

Conclusion: Prolactin may be a risk factor for postmenopausal breast cancer, particularly in the context of postmenopausal hormone use. Investigations of prolactin interactions with other hormonal factors may further inform breast cancer etiology.

Keywords: Breast cancer; Cohort study; Consortium; Postmenopausal breast cancer; Prolactin.

Fig. 1

Plasma prolactin distributions by study sample. Density plots displaying the distributions of plasma prolactin (ng/mL) by study sample. Dotted vertical lines denote the prolactin concentration cut-points for quartile analyses (defined by the distribution of prolactin among all non-cases)

Fig. 2

Non-case distribution of prolactin by participant characteristics. Tests for differences were performed using Kruskal-Wallis analysis of variance tests. Abbreviations: IQR, interquartile range; PMH, postmenopausal hormone; BMI, body mass index; E2, estradiol; PRS, polygenic risk score

Fig. 3

Multivariate-adjusted associations between plasma prolactin (ng/ml) and invasive breast cancer in the pooled sample overall and stratified by time since blood draw. Models adjusted for age, fasting status, PMH use at blood draw, young adult weight, and family history of breast cancer. Abbreviations: CI, confidence interval; SD, standard deviation; p het, p heterogeneity; PMH, postmenopausal hormone

Fig. 4

Multivariable-adjusted associations between plasma prolactin (ng/ml) and invasive breast cancer, stratified by PMH use and BMI at blood draw. Models adjusted for age, fasting status, and PMH use at blood draw (BMI-stratified models only), young adult weight, and family history of breast cancer. Abbreviations: PMH, postmenopausal hormone; BMI, body mass index; CI, confidence interval; p het, p heterogeneity; SD, standard deviation