Grant Number:	1R01CA124865-01A2 Interpret this number
Primary Investigator:	Tamimi, Rulla
Organization:	Brigham And Women'S Hospital
Project Title:	Molecular Predictors of Mammographic Density
Fiscal Year:	2008

DESCRIPTION (provided by applicant): Women with the highest mammographic density are at a four- to six-fold increased risk of breast cancer as compared with women with the lowest mammographic density. The data examining the underlying mechanisms involved are sparse. The widely hypothesized belief that mammographic density reflects cumulative exposure to estrogens has come under question with data from our own group and others. Most studies to date have focused on postmenopausal women, whose levels of estrogens and breast density are both lower than those of premenopausal women. It is highly plausible that mammographic density may be more reflective of premenopausal hormone levels than postmenopausal levels. In addition, a number of other hormones including insulin-like growth factor-1 and vitamin D, and estrogen metabolites have also been implicated in breast proliferation and carcinogenesis and may be associated with breast density. In my first R01 submission, I propose to explore the underlying mechanism by which mammographic density is related to breast cancer, by focusing on circulating hormone levels and urinary estrogen metabolites in premenopausal women. Specifically, we will: (1) Assess the relationship between circulating levels of estrogens, androgens, prolactin, sex hormone binding globulin, vitamin D and insulin-like growth factor-1, and mammographic density; (2) Examine the association between urinary estrogen metabolites in relation to mammographic density; and (3) Determine if hormonal biomarkers and mammographic density are independent predictors of breast cancer risk. These aims will provide complementary information that will help elucidate the biology of mammographic density. We will collect film mammograms and measure breast density among women in a breast cancer case- control study nested within the Nurses' Health Study II for whom blood samples are available and hormone assays will be conducted as part of another funded project. This case-control study is unique in that sex steroid hormones have been measured in both the early follicular and mid-luteal phases of the menstrual cycle. Recent work from our group highlights important differences observed between phase-specific hormone levels and breast cancer risk. To date, no other study has examined phase-specific sex steroids in relation to mammographic density. We expect to have mammographic density as well as hormone measurements on approximately 636 breast cancer cases (361 with timed samples) and 2 matched controls per case. Measurements of both biomarkers and breast density may help to identify women at particularly high risk of breast cancer. This is an efficient study design to determine the association between hormonal biomarkers and mammographic density and the effects of both on breast cancer risk. PUBLIC HEALTH RELEVANCE: Mammographic density and circulating hormone levels are both well-established strong predictors of breast cancer risk. We propose to prospectively examine the association between premenopausal levels of circulating and urinary biomarkers and mammographic density, and determine if these biomarkers and breast density independently predict breast cancer risk. Understanding the relation between the two and how they influence breast cancer risk will be useful in risk prediction and may help to identify women at particularly high risk of breast cancer.




The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.
Authors: Ward S.V. , Burton A. , Tamimi R.M. , Pereira A. , Garmendia M.L. , Pollan M. , Boyd N. , Dos-Santos-Silva I. , Maskarinec G. , Perez-Gomez B. , et al. .
Source: Breast Cancer Research : Bcr, 2022-07-14 00:00:00.0; 24(1), p. 49.
EPub date: 2022-07-14 00:00:00.0.
PMID: 35836268
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Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes.
Authors: Kleinstern G. , Scott C.G. , Tamimi R.M. , Jensen M.R. , Pankratz V.S. , Bertrand K.A. , Norman A.D. , Visscher D.W. , Couch F.J. , Brandt K. , et al. .
Source: Breast Cancer Research And Treatment, 2021-01-04 00:00:00.0; , .
EPub date: 2021-01-04 00:00:00.0.
PMID: 33392844
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Circulating lipids, mammographic density, and risk of breast cancer in the Nurses' Health Study and Nurses' Health Study II.
Authors: Lucht S.A. , Eliassen A.H. , Bertrand K.A. , Ahern T.P. , Borgquist S. , Rosner B. , Hankinson S.E. , Tamimi R.M. .
Source: Cancer Causes & Control : Ccc, 2019-07-01 00:00:00.0; , .
EPub date: 2019-07-01 00:00:00.0.
PMID: 31264139
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Body mass index, mammographic density, and breast cancer risk by estrogen receptor subtype.
Authors: Shieh Y. , Scott C.G. , Jensen M.R. , Norman A.D. , Bertrand K.A. , Pankratz V.S. , Brandt K.R. , Visscher D.W. , Shepherd J.A. , Tamimi R.M. , et al. .
Source: Breast Cancer Research : Bcr, 2019-04-03 00:00:00.0; 21(1), p. 48.
EPub date: 2019-04-03 00:00:00.0.
PMID: 30944014
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Circulating Hormones and Mammographic Density in Premenopausal Women.
Authors: Bertrand K.A. , Eliassen A.H. , Hankinson S.E. , Rosner B.A. , Tamimi R.M. .
Source: Hormones & Cancer, 2018 Apr; 9(2), p. 117-127.
EPub date: 2018-01-12 00:00:00.0.
PMID: 29330698
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Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics.
Authors: Rice M.S. , Tamimi R.M. , Bertrand K.A. , Scott C.G. , Jensen M.R. , Norman A.D. , Visscher D.W. , Chen Y.Y. , Brandt K.R. , Couch F.J. , et al. .
Source: Breast Cancer Research And Treatment, 2018-03-03 00:00:00.0; , .
EPub date: 2018-03-03 00:00:00.0.
PMID: 29502324
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Alcohol consumption across the life course and mammographic density in premenopausal women.
Authors: Liu Y. , Tamimi R.M. , Colditz G.A. , Bertrand K.A. .
Source: Breast Cancer Research And Treatment, 2017-09-26 00:00:00.0; , .
EPub date: 2017-09-26 00:00:00.0.
PMID: 28952004
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Percent mammographic density prediction: development of a model in the nurses' health studies.
Authors: Rice M.S. , Rosner B.A. , Tamimi R.M. .
Source: Cancer Causes & Control : Ccc, 2017 Jul; 28(7), p. 677-684.
EPub date: 2017-05-06 00:00:00.0.
PMID: 28478536
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Mammographic density assessed on paired raw and processed digital images and on paired screen-film and digital images across three mammography systems.
Authors: Burton A. , Byrnes G. , Stone J. , Tamimi R.M. , Heine J. , Vachon C. , Ozmen V. , Pereira A. , Garmendia M.L. , Scott C. , et al. .
Source: Breast Cancer Research : Bcr, 2016-12-19 00:00:00.0; 18(1), p. 130.
EPub date: 2016-12-19 00:00:00.0.
PMID: 27993168
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Mammographic Texture And Risk Of Breast Cancer By Tumor Type And Estrogen Receptor Status
Authors: Malkov S. , Shepherd J.A. , Scott C.G. , Tamimi R.M. , Ma L. , Bertrand K.A. , Couch F. , Jensen M.R. , Mahmoudzadeh A.P. , Fan B. , et al. .
Source: Breast Cancer Research : Bcr, 2016-12-06 00:00:00.0; 18(1), p. 122.
PMID: 27923387
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Mammographic Density And Breast Cancer Risk: A Mediation Analysis
Authors: Rice M.S. , Bertrand K.A. , VanderWeele T.J. , Rosner B.A. , Liao X. , Adami H.O. , Tamimi R.M. .
Source: Breast Cancer Research : Bcr, 2016-09-21 00:00:00.0; 18(1), p. 94.
PMID: 27654859
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International Consortium on Mammographic Density: Methodology and population diversity captured across 22 countries.
Authors: McCormack V.A. , Burton A. , dos-Santos-Silva I. , Hipwell J.H. , Dickens C. , Salem D. , Kamal R. , Hartman M. , Lee C.P. , Chia K.S. , et al. .
Source: Cancer Epidemiology, 2016 Feb; 40, p. 141-51.
PMID: 26724463
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Adolescent Intake Of Animal Fat And Red Meat In Relation To Premenopausal Mammographic Density
Authors: Bertrand K.A. , Burian R.A. , Eliassen A.H. , Willett W.C. , Tamimi R.M. .
Source: Breast Cancer Research And Treatment, 2016 Jan; 155(2), p. 385-93.
PMID: 26791521
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Dense and nondense mammographic area and risk of breast cancer by age and tumor characteristics.
Authors: Bertrand K.A. , Scott C.G. , Tamimi R.M. , Jensen M.R. , Pankratz V.S. , Norman A.D. , Visscher D.W. , Couch F.J. , Shepherd J. , Chen Y.Y. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 May; 24(5), p. 798-809.
PMID: 25716949
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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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Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer.
Authors: Bertrand K.A. , Rosner B. , Eliassen A.H. , Hankinson S.E. , Rexrode K.M. , Willett W. , Tamimi R.M. .
Source: Breast Cancer Research And Treatment, 2015 Jan; 149(2), p. 479-87.
PMID: 25543181
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Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk.
Authors: Lindström S. , Thompson D.J. , Paterson A.D. , Li J. , Gierach G.L. , Scott C. , Stone J. , Douglas J.A. , dos-Santos-Silva I. , Fernandez-Navarro P. , et al. .
Source: Nature Communications, 2014-10-24 00:00:00.0; 5, p. 5303.
EPub date: 2014-10-24 00:00:00.0.
PMID: 25342443
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Mammographic Density Phenotypes And Risk Of Breast Cancer: A Meta-analysis
Authors: Pettersson A. , Graff R.E. , Ursin G. , Santos Silva I.D. , McCormack V. , Baglietto L. , Vachon C. , Bakker M.F. , Giles G.G. , Chia K.S. , et al. .
Source: Journal Of The National Cancer Institute, 2014 May; 106(5), .
PMID: 24816206
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Mammographic Density And Risk Of Breast Cancer By Age And Tumor Characteristics
Authors: Bertrand K.A. , Tamimi R.M. , Scott C.G. , Jensen M.R. , Pankratz V. , Visscher D. , Norman A. , Couch F. , Shepherd J. , Fan B. , et al. .
Source: Breast Cancer Research : Bcr, 2013-11-04 00:00:00.0; 15(6), p. R104.
PMID: 24188089
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Plasma C-peptide, Mammographic Breast Density, And Risk Of Invasive Breast Cancer
Authors: Ahern T.P. , Hankinson S.E. , Willett W.C. , Pollak M.N. , Eliassen A.H. , Tamimi R.M. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2013 Oct; 22(10), p. 1786-96.
PMID: 24097198
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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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Urinary Estrogens And Estrogen Metabolites And Mammographic Density In Premenopausal Women
Authors: Bertrand K.A. , Eliassen A.H. , Hankinson S.E. , Gierach G.L. , Xu X. , Rosner B. , Ziegler R.G. , Tamimi R.M. .
Source: Breast Cancer Research And Treatment, 2012 Nov; 136(1), p. 277-87.
PMID: 23053640
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Breast Fat And Breast Cancer
Authors: Pettersson A. , Tamimi R.M. .
Source: Breast Cancer Research And Treatment, 2012 Aug; 135(1), p. 321-3.
PMID: 22855239
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Body Size Across The Life Course, Mammographic Density, And Risk Of Breast Cancer
Authors: Harris H.R. , Tamimi R.M. , Willett W.C. , Hankinson S.E. , Michels K.B. .
Source: American Journal Of Epidemiology, 2011-10-15 00:00:00.0; 174(8), p. 909-18.
PMID: 21911827
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Nondense Mammographic Area And Risk Of Breast Cancer
Authors: Pettersson A. , Hankinson S.E. , Willett W.C. , Lagiou P. , Trichopoulos D. , Tamimi R.M. .
Source: Breast Cancer Research : Bcr, 2011; 13(5), p. R100.
PMID: 22017857
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