Grant Number:	1R01CA138580-01A2 Interpret this number
Primary Investigator:	Tworoger, Shelley
Organization:	Brigham And Women'S Hospital
Project Title:	Growth Hormones and Breast Cancer Risk
Fiscal Year:	2010

DESCRIPTION (provided by applicant): The relationship between growth factors and breast cancer etiology is complex and not completely understood; however, strong experimental evidence supports their role in breast carcinogenesis. Therefore, in this proposal, we will conduct a detailed evaluation of prolactin and its association with breast cancer risk. This study will use a prospective nested case-control design among pre- or perimenopausal women at blood collection (1,542 cases diagnosed through 2011). Samples were collected in the Nurses' Health Study II (NHSII) in 1996-99 from 29,611 women, ages 32 to 52 years, and in 1989-90 from 32,826 NHS participants, ages 43 to 62 years. In addition to assessing the overall prolactin-breast cancer association, this study will examine whether prolactin is more strongly associated with risk of estrogen receptor positive tumors, as well as tumors staining positive for prolactin, prolactin receptor, cyclin D1, and phosphorylated STAT3 and STAT5. Observing such specificity to the prolactin receptor and its downstream targets would add substantially to the case for causality. Prior studies have assessed prolactin levels using an immunoassay that measures multiple isoforms with differing biologic activities. This study will provide the first prospective assessment of breast cancer risk with a prolactin bioactivity assay, which may better reflect the portion of prolactin that is biologically important. Also, since few correlates of bioactive prolactin are known, this proposal will assess, for the first time, its relationship with known and putative breast cancer risk factors (e.g., parity, shift work). The availability of existing hormone data for this cohort will enable the examination of prolactin as an independent breast cancer risk factor and its interrelationships with other hormones. Importantly, we have added an aim to directly evaluate the addition of prolactin to a comprehensive risk prediction model for breast cancer, which could be useful clinically. Several features of prolactin make it an attractive candidate for inclusion into such models, including that the immunoassay is a standardized and common clinical assay that is very inexpensive and easy to measure. Further, the magnitude of the prolactin association appears to be similar to other factors included in breast cancer risk prediction models. We also will evaluate the inclusion of the bioassay; if this improves prediction better than the immunoassay, it would provide impetus to identify the specific isoforms of prolactin that increase risk of breast cancer and develop inexpensive assays for their measurement. Other grants will provide funding for follow-up and other hormone assays, increasing the cost-effectiveness of this project. Ultimately, elucidating the role of prolactin in breast cancer could open up multiple new areas of research for both treatment and prevention. PUBLIC HEALTH RELEVANCE: The relationship between growth factors and breast cancer etiology is complex and not completely understood; this proposal will extend knowledge about how prolactin, an important growth hormone, is associated with breast cancer risk among premenopausal and perimenopausal women. Characterizing this relationship will provide important knowledge that will translate to prevention and treatment applications. In particular, evaluation of whether prolactin improves risk prediction models could lead to better assessment of women at high risk of breast cancer and more accurate targeting of chemoprevention to these women, given that the Gail model already is utilized clinically and prolactin is an easily measured hormone that is stable across the menstrual cycle and the menopausal transition.




Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers.
Authors: Hathaway C.A. , Rice M.S. , Collins L.C. , Chen D. , Frank D.A. , Walker S. , Clevenger C.V. , Tamimi R.M. , Tworoger S.S. , Hankinson S.E. .
Source: Breast Cancer Research : Bcr, 2023-03-07 00:00:00.0; 25(1), p. 24.
EPub date: 2023-03-07 00:00:00.0.
PMID: 36882838
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Estimating the receiver operating characteristic curve in matched case control studies.
Authors: Xu H. , Qian J. , Paynter N.P. , Zhang X. , Whitcomb B.W. , Tworoger S.S. , Rexrode K.M. , Hankinson S.E. , Balasubramanian R. .
Source: Statistics In Medicine, 2018-11-22 00:00:00.0; , .
EPub date: 2018-11-22 00:00:00.0.
PMID: 30467878
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Circulating prolactin concentrations and risk of type 2 diabetes in US women.
Authors: Li J. , Rice M.S. , Huang T. , Hankinson S.E. , Clevenger C.V. , Hu F.B. , Tworoger S.S. .
Source: Diabetologia, 2018-10-11 00:00:00.0; , .
EPub date: 2018-10-11 00:00:00.0.
PMID: 30306190
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Menstrual cycle characteristics and steroid hormone, prolactin, and growth factor levels in premenopausal women.
Authors: Farland L.V. , Mu F. , Eliassen A.H. , Hankinson S.E. , Tworoger S.S. , Barbieri R.L. , Dowsett M. , Pollak M.N. , Missmer S.A. .
Source: Cancer Causes & Control : Ccc, 2017 Dec; 28(12), p. 1441-1452.
EPub date: 2017-10-31 00:00:00.0.
PMID: 29086892
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Bioactive prolactin levels and risk of breast cancer: a nested case-control study.
Authors: Tworoger S.S. , Rice M.S. , Rosner B.A. , Feeney Y.B. , Clevenger C.V. , Hankinson S.E. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Jan; 24(1), p. 73-80.
PMID: 25315962
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Immunoassay and Nb2 lymphoma bioassay prolactin levels and mammographic density in premenopausal and postmenopausal women the Nurses' Health Studies.
Authors: Rice M.S. , Tworoger S.S. , Bertrand K.A. , Hankinson S.E. , Rosner B.A. , Feeney Y.B. , Clevenger C.V. , Tamimi R.M. .
Source: Breast Cancer Research And Treatment, 2015 Jan; 149(1), p. 245-53.
PMID: 25503962
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Inclusion Of Endogenous Hormone Levels In Risk Prediction Models Of Postmenopausal Breast Cancer
Authors: Tworoger S.S. , Zhang X. , Eliassen A.H. , Qian J. , Colditz G.A. , Willett W.C. , Rosner B.A. , Kraft P. , Hankinson S.E. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2014-10-01 00:00:00.0; 32(28), p. 3111-7.
PMID: 25135988
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A 20-year Prospective Study Of Plasma Prolactin As A Risk Marker Of Breast Cancer Development
Authors: Tworoger S.S. , Eliassen A.H. , Zhang X. , Qian J. , Sluss P.M. , Rosner B.A. , Hankinson S.E. .
Source: Cancer Research, 2013-08-01 00:00:00.0; 73(15), p. 4810-9.
PMID: 23783576
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Insulin-like Growth Factor-1, Insulin-like Growth Factor-binding Protein-3, Growth Hormone, And Mammographic Density In The Nurses' Health Studies
Authors: Rice M.S. , Tworoger S.S. , Rosner B.A. , Pollak M.N. , Hankinson S.E. , Tamimi R.M. .
Source: Breast Cancer Research And Treatment, 2012 Dec; 136(3), p. 805-12.
PMID: 23085768
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