Grant Number:	5R01CA077708-08 Interpret this number
Primary Investigator:	Greendale, Gail
Organization:	University Of California Los Angeles
Project Title:	Sex Steroids & Mammographic Density in the Postmenopause
Fiscal Year:	2007

DESCRIPTION (provided by applicant): Higher mammographic density is an independent risk factor for breast cancer and the magnitude of risk associated with mammographic density is greater than that associated with almost all other known risk factors for breast cancer. This application proposes to continue work in "Sex Steroids and Mammographic Density in the Postmenopause", a study of the effects of endogenous and exogenous sex steroids on mammographic percent-density. This study is an outgrowth of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, which randomly assigned postmenopausal women to placebo, estrogen-only, or one of three combination estrogen/progestin treatments. To date, the principal findings of the "Sex Steroids and Mammographic Density Study" are: 1) Exogenous estrogen-only treatment did not affect mean mammographic density but significant increases in mammographic density did occur in 3 groups assigned to estrogen/progestin treatments; 2) In the three estrogen/progestin groups, but not in the estrogen-only group, the degree of increase in serum estrone level on-treatment predicted the amount of increase in mammographic density; and 3) Endogenous (pre-treatment) serum levels of estrone, estradiol, progesterone, and sex hormone binding globulin were positively associated with baseline mammographic density. Based on these findings, we propose to continue work in this study to gain a further understanding of variation in mammographic density, specifically: 1) What other factors are associated with baseline (pre-treatment) mammographic density? and 2) What additional factors predict increases in mammographic density during treatment? We hypothesize that hormones (in addition to those already studied), genetic polymorphisms in sex steroid biosynthetic/metabolic pathways, and genetic polymorphisms in sex steroid receptors will be related to baseline mammographic density and/or mammographic density response to treatment with hormone therapy. The proposed continuation project will last 4 years and will take place at UCLA and USC. Using stored samples, we will measure baseline and 12-month levels of prolactin and progestins. We will also extract DNA from stored samples to assess selected genetic polymorphisms. The mammographic density outcome data and all relevant covariates have already been measured during our prior work. We will quantify the relations between the hormone and genetic exposures measured in this project and mammographic density (at baseline as well as change in density between baseline and 12 months).




Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study.
Authors: Lee E. , Ingles S.A. , Van Den Berg D. , Wang W. , Lavallee C. , Huang M.H. , Crandall C.J. , Stanczyk F.Z. , Greendale G.A. , Ursin G. .
Source: Menopause (New York, N.Y.), 2012 Mar; 19(3), p. 302-10.
PMID: 22105149
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Predictors of breast discomfort among women initiating menopausal hormone therapy.
Authors: Crandall C.J. , Markovic D. , Huang M.H. , Greendale G.A. .
Source: Menopause (New York, N.Y.), 2010 May-Jun; 17(3), p. 462-70.
PMID: 20009961
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Increases in serum estrone sulfate level are associated with increased mammographic density during menopausal hormone therapy.
Authors: Crandall C.J. , Guan M. , Laughlin G.A. , Ursin G.A. , Stanczyk F.Z. , Ingles S.A. , Barrett-Connor E. , Greendale G.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Jul; 17(7), p. 1674-81.
PMID: 18628419
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Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy.
Authors: Crandall C.J. , Karlamangla A. , Huang M.H. , Ursin G. , Guan M. , Greendale G.A. .
Source: Archives of internal medicine, 2006 Aug 14-28; 166(15), p. 1578-84.
PMID: 16908790
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Positive association between mammographic breast density and bone mineral density in the Postmenopausal Estrogen/Progestin Interventions Study.
Authors: Crandall C. , Palla S. , Reboussin B.A. , Ursin G. , Greendale G.A. .
Source: Breast cancer research : BCR, 2005; 7(6), p. R922-8.
EPub date: 2005-09-22.
PMID: 16280044
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Post-treatment change in serum estrone predicts mammographic percent density changes in women who received combination estrogen and progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
Authors: Ursin G. , Palla S.L. , Reboussin B.A. , Slone S. , Wasilauskas C. , Pike M.C. , Greendale G.A. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2004-07-15; 22(14), p. 2842-8.
PMID: 15254051
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Postmenopausal hormone therapy and change in mammographic density.
Authors: Greendale G.A. , Reboussin B.A. , Slone S. , Wasilauskas C. , Pike M.C. , Ursin G. .
Source: Journal of the National Cancer Institute, 2003-01-01; 95(1), p. 30-7.
PMID: 12509398
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