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Grant Details

Grant Number: 5R01CA067264-14 Interpret this number
Primary Investigator: Trentham-Dietz, Amy
Organization: University Of Wisconsin-Madison
Project Title: Breast Carcinoma in Situ: Predicting Risk and Outcomes
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): As a consequence of widespread screening mammography, approximately 20% of breast cancer diagnosed today is breast carcinoma in situ (BCIS). To reduce the chance of a subsequent breast cancer diagnosis after BCIS, many patients now receive treatment as aggressive as that recommended for invasive breast cancer. Several issues argue for critical examination of the impact of current BCIS detection and treatment practices. These include uncertain risk factors, substantial treatment morbidity, low numbers of BCIS cases that subsequently develop invasive breast cancer, negative impact on quality of life, and importantly, excellent relative survival regardless of therapy choice. A population predictive model, such as the one we have developed for breast cancer epidemiology, can accommodate the multi-dimensional nature of breast cancer. We propose a formal and quantitative evaluation of the uncertainties surrounding BCIS that incorporates multi- level risk factor and screening data into an epidemiologic study and an integrated simulation model assessing the population burden of BCIS. Specifically, we aim to comprehensively examine individual- and geographic- level socioeconomic and screening factors in relation to BCIS disease-free survival and treatment (among cases) and risk (comparing cases and controls). We further aim to use simulation modeling to evaluate the effect of BCIS on breast cancer incidence and outcomes. To accomplish these aims, we will continue to actively follow a large, population-based cohort of BCIS women, comprised of 2,352 cases, for disease-free survival. BCIS cases will be recontacted to ascertain any new breast cancer diagnoses and to evaluate health status and risk factor changes as measured by validated questionnaires. Available data for over 5,000 healthy population controls previously enrolled for our case-control studies will be included in case-control analyses jointly considering individual-level and geographic factors. Using epidemiologic data from the BCIS cases and controls as inputs, we will enhance our validated breast cancer discrete-event simulation model with individual- level risk factors, geographic measures of screening and treatment, and tumor histology. We will use the model to assess the contribution of BCIS diagnosis and treatment towards recent declines in breast cancer incidence and mortality rates since the 1990s, and to evaluate quality-adjusted life years resulting from screening and treatment regimens. Records from Wisconsin's statewide tumor registry, interview information, and publicly available data linked to the BCIS cases and controls through their geocoded residential addresses will contribute to both the epidemiologic cohort and case-control analyses and the simulation model. Using epidemiologic studies and computer modeling, this study will address BCIS uncertainties by characterizing the multitude of factors related to BCIS incidence, choice of treatment, quality of life, disease-free survival, and mortality. This study will efficiently and validly provide broad perspectives on BCIS, an increasingly important public health concern. PUBLIC HEALTH RELEVANCE: Women who are diagnosed with breast carcinoma in situ (BCIS) - 20% of all breast cancer diagnoses - have an excellent prognosis regardless of the type of therapy they receive. However, since women with BCIS are often treated with aggressive therapy and suffer similar side effects as women with more invasive cancer, the overall impact of BCIS detection and treatment on length and quality of life is not clear. The long-term goal of this project is to reduce the public health impact of BCIS by quantifying both contextual and personal risk factors for the development of BCIS and the recurrence of breast cancer after a BCIS diagnosis.

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Publications

Disease-free survival by treatment after a DCIS diagnosis in a population-based cohort study.
Authors: Sprague BL, McLaughlin V, Hampton JM, Newcomb PA, Trentham-Dietz A
Source: Breast Cancer Res Treat, 2013 Aug;141(1), p. 145-54.
EPub date: 2013 Aug 25.
PMID: 23979007
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Selection bias in population-based cancer case-control studies due to incomplete sampling frame coverage.
Authors: Walsh MC, Trentham-Dietz A, Gangnon RE, Nieto FJ, Newcomb PA, Palta M
Source: Cancer Epidemiol Biomarkers Prev, 2012 Jun;21(6), p. 881-6.
EPub date: 2012 Apr 6.
PMID: 22490319
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Availability of driver's license master lists for use in government-sponsored public health research.
Authors: Walsh MC, Trentham-Dietz A, Palta M
Source: Am J Epidemiol, 2011 Jun 15;173(12), p. 1414-8.
EPub date: 2011 May 13.
PMID: 21571870
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Change in lifestyle behaviors and medication use after a diagnosis of ductal carcinoma in situ.
Authors: Sprague BL, Trentham-Dietz A, Nichols HB, Hampton JM, Newcomb PA
Source: Breast Cancer Res Treat, 2010 Nov;124(2), p. 487-95.
EPub date: 2010 Apr 2.
PMID: 20361251
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Association of COMT haplotypes and breast cancer risk in caucasian women.
Authors: Peterson NB, Trentham-Dietz A, Garcia-Closas M, Newcomb PA, Titus-Ernstoff L, Huang Y, Chanock SJ, Haines JL, Egan KM
Source: Anticancer Res, 2010 Jan;30(1), p. 217-20.
PMID: 20150638
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Prevalence of breast carcinoma in situ in the United States.
Authors: Sprague BL, Trentham-Dietz A
Source: JAMA, 2009 Aug 26;302(8), p. 846-8.
PMID: 19706857
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Tea consumption and risk of breast cancer.
Authors: Kumar N, Titus-Ernstoff L, Newcomb PA, Trentham-Dietz A, Anic G, Egan KM
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jan;18(1), p. 341-5.
PMID: 19124518
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Oral contraceptive use and risk of breast carcinoma in situ.
Authors: Nichols HB, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Hampton JM, Newcomb PA
Source: Cancer Epidemiol Biomarkers Prev, 2007 Nov;16(11), p. 2262-8.
PMID: 18006914
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Cigarette smoking and risk of breast carcinoma in situ.
Authors: Trentham-Dietz A, Nichols HB, Egan KM, Titus-Ernstoff L, Hampton JM, Newcomb PA
Source: Epidemiology, 2007 Sep;18(5), p. 629-38.
PMID: 17700252
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Genetic variation in TP53 and risk of breast cancer in a population-based case control study.
Authors: Sprague BL, Trentham-Dietz A, Garcia-Closas M, Newcomb PA, Titus-Ernstoff L, Hampton JM, Chanock SJ, Haines JL, Egan KM
Source: Carcinogenesis, 2007 Aug;28(8), p. 1680-6.
EPub date: 2007 Apr 21.
PMID: 17449902
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Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk.
Authors: Gaudet MM, Egan KM, Lissowska J, Newcomb PA, Brinton LA, Titus-Ernstoff L, Yeager M, Chanock S, Welch R, Peplonska B, Trentham-Dietz A, Garcia-Closas M
Source: Hum Genet, 2007 May;121(3-4), p. 483-90.
EPub date: 2007 Jan 11.
PMID: 17216494
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Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium.
Authors: Breast Cancer Association Consortium
Source: J Natl Cancer Inst, 2006 Oct 4;98(19), p. 1382-96.
PMID: 17018785
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Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer.
Authors: Zhang Y, Newcomb PA, Egan KM, Titus-Ernstoff L, Chanock S, Welch R, Brinton LA, Lissowska J, Bardin-Mikolajczak A, Peplonska B, Szeszenia-Dabrowska N, Zatonski W, Garcia-Closas M
Source: Cancer Epidemiol Biomarkers Prev, 2006 Feb;15(2), p. 353-8.
PMID: 16492928
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Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses.
Authors: García-Closas M, Egan KM, Newcomb PA, Brinton LA, Titus-Ernstoff L, Chanock S, Welch R, Lissowska J, Peplonska B, Szeszenia-Dabrowska N, Zatonski W, Bardin-Mikolajczak A, Struewing JP
Source: Hum Genet, 2006 May;119(4), p. 376-88.
EPub date: 2006 Feb 17.
PMID: 16485136
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Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash.
Authors: García-Closas M, Egan KM, Abruzzo J, Newcomb PA, Titus-Ernstoff L, Franklin T, Bender PK, Beck JC, Le Marchand L, Lum A, Alavanja M, Hayes RB, Rutter J, Buetow K, Brinton LA, Rothman N
Source: Cancer Epidemiol Biomarkers Prev, 2001 Jun;10(6), p. 687-96.
PMID: 11401920
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