Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.
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The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.
Aged, 80 and over
Carcinoma, Ductal, Breast
Continental Population Groups
Published Version (Please cite this version)10.1007/s10549-011-1347-z
Publication InfoKravchenko, J; Akushevich, Igor; Seewaldt, Victoria Louise; Abernethy, Amy Pickar; & Lyerly, Herbert Kim (2011). Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms. Breast Cancer Res Treat, 128(2). pp. 483-493. 10.1007/s10549-011-1347-z. Retrieved from http://hdl.handle.net/10161/14852.
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Adjunct Professor in the Department of Medicine
Amy P. Abernethy, MD PhDDirector, Center for Learning Health Care Director, Duke Cancer Care Research Program Professor of Medicine, Department of Medicine, Division of Medical Oncology, Duke University School of Medicine Associate Professor of Nursing, Duke University School of NursingDr. Abernethy, a hematologist/oncologist and palliative care physician, is Professor of Medicine in the Duke University School of Medicine, Director of the Duke Center for Learn
Associate Research Professor in the Social Science Research Institute
George Barth Geller Professor
Professor of Medicine
Victoria Seewaldt, M.D. Priority #1: Microenvironment in Early Mammary Carcinogenesis: Role of extracellular matrix signaling: Interactions between normal human mammary epithelial cells (HMECs) and extracellular matrix (ECM) play a critical role in maintaining normal tissue homeostasis and are likely disrupted during the initiation of breast cancer. We developed several in vitro systems to test the hypothesis that ECM-growth regulatory and –polarity
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