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    Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

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    Date
    2011-07
    Authors
    Kravchenko, J
    Akushevich, Igor
    Seewaldt, Victoria Louise
    Abernethy, Amy Pickar
    Lyerly, Herbert Kim
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    Abstract
    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.
    Type
    Journal article
    Subject
    Adult
    Age Factors
    Aged
    Aged, 80 and over
    Breast Neoplasms
    Carcinoma, Ductal, Breast
    Carcinoma, Lobular
    Continental Population Groups
    Female
    Humans
    Incidence
    Middle Aged
    Neoplasm Staging
    North Carolina
    Prognosis
    Receptor, ErbB-2
    Receptors, Estrogen
    Receptors, Progesterone
    Risk Factors
    SEER Program
    Permalink
    https://hdl.handle.net/10161/14852
    Published Version (Please cite this version)
    10.1007/s10549-011-1347-z
    Publication Info
    Kravchenko, 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 https://hdl.handle.net/10161/14852.
    This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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    Scholars@Duke

    Abernethy

    Amy Pickar Abernethy

    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
    This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.

    Igor Akushevich

    Associate Research Professor in the Social Science Research Institute
    Lyerly

    Herbert Kim Lyerly

    George Barth Geller Distinguished Professor

    Victoria Louise Seewaldt

    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
    This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
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