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      Plasma prolactin and breast cancer risk: a meta- analysis

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          Abstract

          Breast cancer is the most common cancer among women, and its incidence is on a constant rise. Previous studies suggest that higher levels of plasma prolactin are associated with escalated risk of breast cancer, however, these results are contradictory and inconclusive. PubMed and Medline were used to search and identify published observational studies that assessed the relationship between plasma prolactin levels and the risk of breast cancer. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model. A total of 7 studies were included in our analysis. For the highest versus lowest levels of plasma prolactin, the pooled RR (95% CI) of breast cancer were 1.16 (1.04, 1.29). In subgroup analyses, we found a positive association between plasma prolactin levels and the risk of breast cancer among the patients who were postmenopausal, ER +/PR + or in situ and invasive carcinoma. However, this positive association was not detected in the premenopausal and ER -/PR - patients. In conclusion, the present study provides evidence supporting a significantly positive association between plasma prolactin levels and the risk of breast cancer.

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          Mammary gland development.

          Hector Macias, Lindsay Hinck (2012)
          The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.
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            A 20-year prospective study of plasma prolactin as a risk marker of breast cancer development.

            Shelley S. Tworoger, A. Eliassen, Xuehong Zhang … (2013)
            Understanding how the timing of exposure to endogenous hormones influences cancer development is critical to elucidating disease etiology. Prolactin increases proliferation and cell motility, processes important in later stage tumor development, suggesting that levels proximate (versus distant) to diagnosis may better predict risk. Thus, we calculated relative risks (RR) and 95% confidence intervals (CI) for prolactin levels on samples collected 10 years before diagnosis/reference date. There was an increased risk for higher proximate prolactin levels [RR, >15.7 vs. ≤8.1 ng/mL (i.e., top vs. bottom quartiles) = 1.20; 95% CI, 1.03-1.40; Ptrend = 0.005], but not for distant levels (RR = 0.97; Ptrend = 0.94); results were similar among women with two blood samples (Pinteraction, proximate vs. distant = 0.07). The positive association was stronger for ER(+) disease (RR = 1.28; Ptrend = 0.003) and postmenopausal women (RR = 1.37; Ptrend = 0.0002). Among postmenopausal women, the association was strongest for ER(+) disease (RR = 1.52) and lymph node-positive cases (RR = 1.63). Our data suggest that prolactin levels measured <10 years before diagnosis are most strongly associated with postmenopausal breast cancer risk, especially for ER(+) tumors and metastatic disease. This corresponds with biologic data that prolactin is etiologically important in tumor promotion. ©2013 AACR.
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              Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women.

              Shelley S. Tworoger, P Sluss, Sue Hankinson (2006)
              Recent evidence suggests that prolactin may be positively associated with postmenopausal breast cancer risk; however, little data are available in younger women. Therefore, we conducted a prospective, nested case-control study to examine the relationship between plasma prolactin concentrations and breast cancer risk in predominately premenopausal women from the Nurses' Health Study II. Blood samples were collected from 1996 to 1999. The analysis includes 316 cases of breast cancer diagnosed after blood donation and before June 1, 2003, who had two controls matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. Sixty-three percent of participants provided a timed follicular and luteal menstrual phase blood sample; other women provided a single untimed sample. When including all women, we observed a positive association between prolactin and breast cancer risk [relative risk (RR), top quartile versus bottom quartile, 1.5; 95% confidence interval (95% CI), 1.0-2.3; P(trend) = 0.03] that was slightly stronger among estrogen receptor-positive/progesterone receptor-positive tumors (comparable RR, 1.9; 95% CI, 1.1-3.3; P(trend) = 0.04). Associations were similar among premenopausal women only. However, we did not find an association between prolactin and breast cancer risk among the subset of women who only provided timed samples (comparable RR, average of timed samples, 1.3; 95% CI, 0.8-2.3; P(trend) = 0.40). The association seemed stronger among women > or = 45 years old and for cases diagnosed within approximately 4 years of blood collection. Our data suggest a modest positive association between prolactin and breast cancer risk among predominately premenopausal women; however, further follow-up is needed to increase power for subgroup analyses.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 17 May 2016
                Publication date Collection: 2016
                Volume: 6
                Electronic Location Identifier: 25998
                Affiliations
                [1 ]Breast Disease Center, Southwest Hospital, Third Military Medical University , Chongqing, 400038, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                Publisher Item ID: srep25998
                DOI: 10.1038/srep25998
                PMC ID: 4869065
                PubMed ID: 27184120
                SO-VID: 0460cb78-9c1c-4d86-8de7-67cc4035b02e
                Copyright © Copyright © 2016, Macmillan Publishers Limited
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                Date received : 06 January 2016
                Date accepted : 25 April 2016
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