Elevated rates of DCIS diagnoses are inherent to current breast cancer screening processes - almost 30% of screen-detected breast cancers are DCIS. Due to uncertainty in the natural history of DCIS, there is widespread concern regarding overtreatment. Unfortunately, it is currently impossible to determine which DCIS lesions are likely to progress to a potentially lethal invasive stage. Thus, current guidelines recommend relatively aggressive treatment for all women with DCIS, including surgery, radiation, and consideration of hormone therapy. To optimize the breast cancer screening process, there is an urgent need for identification of DCIS prognostic markers that would permit personalized treatment strategies. Mammographic breast density is a promising candidate as a prognostic marker to predict the likelihood of progression from DCIS to invasive disease. Currently, however, there Is only scarce data regarding the nature of the association between breast density and disease progression, and much uncertainty in our understanding of the biological mechanisms of breast density. Collagen is a major component of breast density and laboratory studies have shown that it plays a key role in facilitating tumor Invasion. The objective of our proposal is to translate these laboratory findings into advances in the development of breast density as a prognostic marker for DCIS.
We aim to 1) determine the association between mammographic breast density and disease-free survival among women with DCIS;2) determine the association between collagen reorganization and disease-free survival among women with DCIS;and 3) assess whether the association between mammographic breast density and disease-free survival is mediated by collagen reorganization. To accomplish these aims, we will use data and tissue from the Vermont Breast Cancer Surveillance System, which includes linked patient risk factor, mammography, pathology, treatment, and cancer outcomes data for approximately 1,400 DCIS cases with up to 16 years of follow-up. We will use three different measures of breast density: the categorical BIF^DS assessment, a 2-D quantitative computer-assisted method (Cumulus), and a 3-D quantitative volumetric density assessment that permits measurement of breast density in specific regions of interest adjacent to the DCIS lesion. Multiphoton microscopy will be used to evaluate collagen reorganization in archived DCIS tumor specimens. This study will evaluate the potential for mammographic breast density and collagen reorganization to serve as potential markers for identifying DCIS cases that are not likely to progress or could be treated with only minimal intervention. This could lead to a substantial improvement in our ability to minimize the harms of breast cancer screening (overtreatment) while preserving the benefits (reductions in breast cancer morbidity and mortality).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRLB-R)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Vermont & St Agric College
United States
Zip Code
Onega, Tracy; Lee, Christoph I; Benkeser, David et al. (2016) Travel Burden to Breast MRI and Utilization: Are Risk and Sociodemographics Related? J Am Coll Radiol 13:611-9
Carney, Patricia A; Allison, Kimberly H; Oster, Natalia V et al. (2016) Identifying and processing the gap between perceived and actual agreement in breast pathology interpretation. Mod Pathol 29:717-26
Corley, Douglas A; Haas, Jennifer S; Kobrin, Sarah (2016) Reducing Variation in the ""Standard of Care"" for Cancer Screening: Recommendations From the PROSPR Consortium. JAMA 315:2067-8
Hubbard, Rebecca A; Ripping, Theodora M; Chubak, Jessica et al. (2016) Statistical Methods for Estimating the Cumulative Risk of Screening Mammography Outcomes. Cancer Epidemiol Biomarkers Prev 25:513-20
Mandelblatt, Jeanne S; Stout, Natasha K; Schechter, Clyde B et al. (2016) Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies. Ann Intern Med 164:215-25
Schapira, Marilyn M; Sprague, Brian L; Klabunde, Carrie N et al. (2016) Inadequate Systems to Support Breast and Cervical Cancer Screening in Primary Care Practice. J Gen Intern Med 31:1148-55
Sprague, Brian L; Conant, Emily F; Onega, Tracy et al. (2016) Variation in Mammographic Breast Density Assessments Among Radiologists in Clinical Practice: A Multicenter Observational Study. Ann Intern Med 165:457-464
Hubbard, Rebecca A; O'Meara, Ellen S; Henderson, Louise M et al. (2016) Multilevel factors associated with long-term adherence to screening mammography in older women in the U.S. Prev Med 89:169-77
Klabunde, Carrie N; Zheng, Yingye; Quinn, Virginia P et al. (2016) Influence of Age and Comorbidity on Colorectal Cancer Screening in the Elderly. Am J Prev Med 51:e67-75
Valeri, Linda; Chen, Jarvis T; Garcia-Albeniz, Xabier et al. (2016) The Role of Stage at Diagnosis in Colorectal Cancer Black-White Survival Disparities: A Counterfactual Causal Inference Approach. Cancer Epidemiol Biomarkers Prev 25:83-9

Showing the most recent 10 out of 55 publications