Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers

• Type of Material: Article
• Authors: Cassandra A Hathaway, Moffitt Cancer Center; Meggan S Rice, Massachusetts General Hospital; Laura C Collins, Harvard Medical School; Dilys Chen, Harvard Medical School; David Frank, Emory University; Sarah Walker, Harvard Medical School; Charles V Clevenger, Virginia Commonwealth University; Rulla M Tamimi, Weill Cornell Medicine; Shelley S Tworoger, Moffitt Cancer Center; Susan E Hankinson, University of Massachusetts, Amherst
• Language: English
• Date: 2023-03-07
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13058-023-01618-3
• Title of Journal or Parent Work: BREAST CANCER RESEARCH
• Volume: 25
• Issue: 1
• Start Page: 24
• End Page: 24
• Grant/Funding Information: This study was supported by research grants from the National Cancer Institute, National Institutes of Health, UM1 CA186107, P01 CA87969, R01 CA49449, U01 CA176726, R01 CA67262, R01 CA138580, UM1 CA176726, T32 CA009001. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors assume full responsibility for analyses and interpretation of these data.
• Keywords: Breast cancer; STAT-JAK; ROLES; Science & Technology; Oncology; Life Sciences & Biomedicine; Risk; PLASMA PROLACTIN; SURVIVAL; Prolactin; THERAPY; PROLIFERATION; STAT5; PROTEINS; DIFFERENTIATION; ACTIVATION; NUCLEAR JAK2
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Pathology; Health Sciences, Oncology

Abstract

Background: Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRLR, STAT5, and the upstream kinase JAK2. Methods: Using data from 745 cases and 2454 matched controls in the Nurses’ Health Study, we conducted polytomous logistic regression to examine the association between prolactin (> 11 ng/mL vs. ≤ 11 ng/mL) measured within 10 years of diagnosis and breast cancer risk by PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), and phosphorylated JAK2 (pJAK2; C) tumor expression. Analyses were conducted separately in premenopausal (n = 168 cases, 765 controls) and postmenopausal women (n = 577 cases, 1689 controls). Results: In premenopausal women, prolactin levels > 11 ng/mL were positively associated with risk of tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02–5.22) and pSTAT5-C (OR 1.64, 95% CI 1.01–2.65), but not tumors that were negative for these markers (OR 0.98, 95% CI 0.65–1.46 and OR 0.73, 95% CI 0.43–1.25; p-heterogeneity = 0.06 and 0.02, respectively). This was stronger when tumors were positive for both pSTAT5-N and pSTAT5-C (OR 2.88, 95% CI 1.14–7.25). No association was observed for PRLR or pJAK2 (positive or negative) and breast cancer risk among premenopausal women. Among postmenopausal women, plasma prolactin levels were positively associated with breast cancer risk irrespective of PRLR, pSTAT5, or pJAK2 expression (all p-heterogeneity ≥ 0.21). Conclusion: We did not observe clear differences in the association between plasma prolactin and breast cancer risk by tumor expression of PRLR or pJAK2, although associations for premenopausal women were observed for pSTAT5 positive tumors only. While additional studies are needed, this suggests that prolactin may act on human breast tumor development through alternative pathways.