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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA067264-13
Application #
8210926
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Shelburne, Nonniekaye F
Project Start
1996-06-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
13
Fiscal Year
2012
Total Cost
$339,702
Indirect Cost
$108,480
Name
University of Wisconsin Madison
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
McLaughlin, Vicki Hart; Trentham-Dietz, Amy; Hampton, John M et al. (2014) Lifestyle factors and the risk of a second breast cancer after ductal carcinoma in situ. Cancer Epidemiol Biomarkers Prev 23:450-60
Sprague, Brian L; McLaughlin, Vicki; Hampton, John M et al. (2013) Disease-free survival by treatment after a DCIS diagnosis in a population-based cohort study. Breast Cancer Res Treat 141:145-54
Mandelblatt, Jeanne S; Stout, Natasha; Trentham-Dietz, Amy (2011) To screen or not to screen women in their 40s for breast cancer: is personalized risk-based screening the answer? Ann Intern Med 155:58-60
Nichols, Hazel B; Visvanathan, Kala; Newcomb, Polly A et al. (2011) Bilateral oophorectomy in relation to risk of postmenopausal breast cancer: confounding by nonmalignant indications for surgery? Am J Epidemiol 173:1111-20
Walsh, Matthew C; Trentham-Dietz, Amy; Palta, Mari (2011) Availability of driver's license master lists for use in government-sponsored public health research. Am J Epidemiol 173:1414-8
Sprague, Brian L; Trentham-Dietz, Amy; Remington, Patrick L (2011) The contribution of postmenopausal hormone use cessation to the declining incidence of breast cancer. Cancer Causes Control 22:125-34
Sprague, Brian L; Trentham-Dietz, Amy; Nichols, Hazel B et al. (2010) Change in lifestyle behaviors and medication use after a diagnosis of ductal carcinoma in situ. Breast Cancer Res Treat 124:487-95
Sprague, Brian L; Trentham-Dietz, Amy; Burnside, Elizabeth S (2010) Socioeconomic disparities in the decline in invasive breast cancer incidence. Breast Cancer Res Treat 122:873-8
Peterson, Neeraja B; Trentham-Dietz, Amy; Garcia-Closas, Montserrat et al. (2010) Association of COMT haplotypes and breast cancer risk in caucasian women. Anticancer Res 30:217-20
Sprague, Brian L; Trentham-Dietz, Amy (2009) Prevalence of breast carcinoma in situ in the United States. JAMA 302:846-8

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