Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.
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 articleSubject
AdultAge 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
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https://hdl.handle.net/10161/14852Published Version (Please cite this version)
10.1007/s10549-011-1347-zPublication 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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Show full item recordScholars@Duke
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
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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