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Grant Details

Grant Number: 5R01CA140286-05 Interpret this number
Primary Investigator: Vachon, Celine
Organization: Mayo Clinic Rochester
Project Title: Risk Factors for Breast Cancer Molecular Subtypes
Fiscal Year: 2014
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Abstract

Abstract Recently, gene expression profiling has identified molecular subtypes that classify invasive breast cancers into distinct categories that vary in their clinical behavior and response to treatment. These subtypes highlight the many possible biologically and clinically distinct types of breast cancer. With such heterogeneity within breast cancer, we might expect that risk factors influence specific subtypes of breast cancer through different etiologic pathways. Mammographic density (MD), the proportion of the white or dense regions on a mammogram, has been shown to be one of the strongest and most consistent risk factors for breast cancer. We propose a large collaboration of four established cohort studies [Nurses' Health Study (I and II) Blood Subcohorts, Mayo Mammography Health Study and San Francisco Mammography Registry/UCSF SPORE] with similar methods for ascertaining risk factors, MD, breast cancer and breast cancer subtype information, to examine the association of MD with subtypes of invasive breast cancer. Specifically, we propose Aim 1) To ascertain and combine clinical risk factor, MD and breast cancer information to create a large nested case-control study of ~3300 women with invasive breast cancer and ~5700 matched controls, Aim 2) To characterize breast cancer subtypes for all invasive breast cancers using information from pathology reports, cancer registries and pathologic review. We propose to classify cancers according to hormone receptors (estrogen (ER) and progesterone (PR)), human epidermal growth factor-2 (HER2) expression, tumor size, nodal involvement, histologic subtype and grade. Also, using both clinically available information and results from immunohistochemistry and FISH analyses, we will classify cancers into the 'intrinsic' molecular subtypes defined as Luminal A, Luminal B, Basal-like, HER2-expressing and Unclassified. Aim 3) To evaluate the association of MD with each of the histologic and molecular breast cancer subtypes defined in Aim 2, and Aim 4) To combine MD and clinical breast cancer risk factor information to develop a risk prediction model for breast cancer and the specific breast cancer molecular subtypes. Our secondary aim will examine associations of novel parenchyma features of digitized mammogram films with breast cancer and histologic and molecular breast cancer subtypes. Successful completion of this protocol will 1) address the question whether MD is associated with breast cancer subtypes, 2) result in a new risk prediction model for breast cancer and molecular subtypes, and 3) establish a large, collaborative nested-case control study with risk factors, MD, and well-annotated breast cancers that can be used for future studies. Identifying whether MD is associated with specific subtypes of breast cancer may result in more targeted prevention and surveillance strategies for women with high MD. Also, risk models for the molecular subtypes incorporating MD and parenchyma measures will likely be more informative than those treating breast cancer as one disease.

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Publications

Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes.
Authors: Yaghjyan L. , Esnakula A.K. , Scott C.G. , Wijayabahu A.T. , Jensen M.R. , Vachon C.M. .
Source: Cancer causes & control : CCC, 2019-07-27; , .
EPub date: 2019-07-27.
PMID: 31352658
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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; 21(1), p. 48.
EPub date: 2019-04-03.
PMID: 30944014
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Shared heritability and functional enrichment across six solid cancers.
Authors: Jiang X. , Finucane H.K. , Schumacher F.R. , Schmit S.L. , Tyrer J.P. , Han Y. , Michailidou K. , Lesseur C. , Kuchenbaecker K.B. , Dennis J. , et al. .
Source: Nature communications, 2019-01-25; 10(1), p. 431.
EPub date: 2019-01-25.
PMID: 30683880
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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 Jul; 170(1), p. 129-141.
EPub date: 2018-03-03.
PMID: 29502324
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Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
Authors: Milne R.L. , Kuchenbaecker K.B. , Michailidou K. , Beesley J. , Kar S. , Lindstr÷m S. , Hui S. , Lemašon A. , Soucy P. , Dennis J. , et al. .
Source: Nature genetics, 2017 Dec; 49(12), p. 1767-1778.
EPub date: 2017-10-23.
PMID: 29058716
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Association analysis identifies 65 new breast cancer risk loci.
Authors: Michailidou K. , Lindstr÷m S. , Dennis J. , Beesley J. , Hui S. , Kar S. , Lemašon A. , Soucy P. , Glubb D. , Rostamianfar A. , et al. .
Source: Nature, 2017-11-02; 551(7678), p. 92-94.
EPub date: 2017-10-23.
PMID: 29059683
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Interaction of mammographic breast density with menopausal status and postmenopausal hormone use in relation to the risk of aggressive breast cancer subtypes.
Authors: Yaghjyan L. , Tamimi R.M. , Bertrand K.A. , Scott C.G. , Jensen M.R. , Pankratz V.S. , Brandt K. , Visscher D. , Norman A. , Couch F. , et al. .
Source: Breast cancer research and treatment, 2017 Sep; 165(2), p. 421-431.
EPub date: 2017-06-17.
PMID: 28624977
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Tissue-based associations of mammographic breast density with breast stem cell markers.
Authors: Yaghjyan L. , Stoll E. , Ghosh K. , Scott C.G. , Jensen M.R. , Brandt K.R. , Visscher D. , Vachon C.M. .
Source: Breast cancer research : BCR, 2017-08-29; 19(1), p. 100.
EPub date: 2017-08-29.
PMID: 28851411
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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; 18(1), p. 130.
EPub date: 2016-12-19.
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; 18(1), p. 122.
EPub date: 2016-12-06.
PMID: 27923387
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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.
EPub date: 2015-12-24.
PMID: 26724463
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A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density.
Authors: Rudolph A. , Fasching P.A. , Behrens S. , Eilber U. , Bolla M.K. , Wang Q. , Thompson D. , Czene K. , Brand J.S. , Li J. , et al. .
Source: Breast cancer research : BCR, 2015-08-16; 17, p. 110.
EPub date: 2015-08-16.
PMID: 26275715
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The contributions of breast density and common genetic variation to breast cancer risk.
Authors: Vachon C.M. , Pankratz V.S. , Scott C.G. , Haeberle L. , Ziv E. , Jensen M.R. , Brandt K.R. , Whaley D.H. , Olson J.E. , Heusinger K. , et al. .
Source: Journal of the National Cancer Institute, 2015 May; 107(5), .
EPub date: 2015-03-04.
PMID: 25745020
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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.
EPub date: 2015-02-25.
PMID: 25716949
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Automated Percentage of Breast Density Measurements for Full-field Digital Mammography Applications.
Authors: Fowler E.E. , Vachon C.M. , Scott C.G. , Sellers T.A. , Heine J.J. .
Source: Academic radiology, 2014 Aug; 21(8), p. 958-70.
PMID: 25018067
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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, 2014-05-10; 106(5), .
EPub date: 2014-05-10.
PMID: 24816206
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Mammographic texture resemblance generalizes as an independent risk factor for breast cancer.
Authors: Nielsen M. , Vachon C.M. , Scott C.G. , Chernoff K. , Karemore G. , Karssemeijer N. , Lillholm M. , Karsdal M.A. .
Source: Breast cancer research : BCR, 2014-04-08; 16(2), p. R37.
EPub date: 2014-04-08.
PMID: 24713478
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A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis.
Authors: Reese S.E. , Archer K.J. , Therneau T.M. , Atkinson E.J. , Vachon C.M. , de Andrade M. , Kocher J.P. , Eckel-Passow J.E. .
Source: Bioinformatics (Oxford, England), 2013-11-15; 29(22), p. 2877-83.
EPub date: 2013-08-19.
PMID: 23958724
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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; 15(6), p. R104.
EPub date: 2013-11-04.
PMID: 24188089
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Benign breast disease, mammographic breast density, and the risk of breast cancer.
Authors: Tice J.A. , O'Meara E.S. , Weaver D.L. , Vachon C. , Ballard-Barbash R. , Kerlikowske K. .
Source: Journal of the National Cancer Institute, 2013-07-17; 105(14), p. 1043-9.
EPub date: 2013-06-06.
PMID: 23744877
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Mammographic breast density response to aromatase inhibition.
Authors: Vachon C.M. , Suman V.J. , Brandt K.R. , Kosel M.L. , Buzdar A.U. , Olson J.E. , Wu F.F. , Flickinger L.M. , Ursin G. , Elliott C.R. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2013-04-15; 19(8), p. 2144-53.
EPub date: 2013-03-06.
PMID: 23468058
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Comparison of percent density from raw and processed full-field digital mammography data.
Authors: Vachon C.M. , Fowler E.E. , Tiffenberg G. , Scott C.G. , Pankratz V.S. , Sellers T.A. , Heine J.J. .
Source: Breast cancer research : BCR, 2013-01-04; 15(1), p. R1.
EPub date: 2013-01-04.
PMID: 23289950
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The influence of mammogram acquisition on the mammographic density and breast cancer association in the Mayo Mammography Health Study cohort.
Authors: Olson J.E. , Sellers T.A. , Scott C.G. , Schueler B.A. , Brandt K.R. , Serie D.J. , Jensen M.R. , Wu F.F. , Morton M.J. , Heine J.J. , et al. .
Source: Breast cancer research : BCR, 2012-11-15; 14(6), p. R147.
EPub date: 2012-11-15.
PMID: 23152984
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Do fatty breasts increase or decrease breast cancer risk?
Authors: Shepherd J.A. , Kerlikowske K. .
Source: Breast cancer research : BCR, 2012-01-25; 14(1), p. 102.
EPub date: 2012-01-25.
PMID: 22277587
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Tissue composition of mammographically dense and non-dense breast tissue.
Authors: Ghosh K. , Brandt K.R. , Reynolds C. , Scott C.G. , Pankratz V.S. , Riehle D.L. , Lingle W.L. , Odogwu T. , Radisky D.C. , Visscher D.W. , et al. .
Source: Breast cancer research and treatment, 2012 Jan; 131(1), p. 267-75.
EPub date: 2011-08-30.
PMID: 21877142
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Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics.
Authors: Yaghjyan L. , Colditz G.A. , Collins L.C. , Schnitt S.J. , Rosner B. , Vachon C. , Tamimi R.M. .
Source: Journal of the National Cancer Institute, 2011-08-03; 103(15), p. 1179-89.
EPub date: 2011-07-27.
PMID: 21795664
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