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

dc.contributor.author Kravchenko, J
dc.contributor.author Akushevich, Igor
dc.contributor.author Seewaldt, Victoria Louise
dc.contributor.author Abernethy, Amy Pickar
dc.contributor.author Lyerly, Herbert Kim
dc.coverage.spatial Netherlands
dc.date.accessioned 2017-06-06T17:13:50Z
dc.date.available 2017-06-06T17:13:50Z
dc.date.issued 2011-07
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/21225455
dc.identifier.uri http://hdl.handle.net/10161/14852
dc.description.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.
dc.language eng
dc.relation.ispartof Breast Cancer Res Treat
dc.relation.isversionof 10.1007/s10549-011-1347-z
dc.subject Adult
dc.subject Age Factors
dc.subject Aged
dc.subject Aged, 80 and over
dc.subject Breast Neoplasms
dc.subject Carcinoma, Ductal, Breast
dc.subject Carcinoma, Lobular
dc.subject Continental Population Groups
dc.subject Female
dc.subject Humans
dc.subject Incidence
dc.subject Middle Aged
dc.subject Neoplasm Staging
dc.subject North Carolina
dc.subject Prognosis
dc.subject Receptor, ErbB-2
dc.subject Receptors, Estrogen
dc.subject Receptors, Progesterone
dc.subject Risk Factors
dc.subject SEER Program
dc.title Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/21225455
pubs.begin-page 483
pubs.end-page 493
pubs.issue 2
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Duke Population Research Institute
pubs.organisational-group Faculty
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Nursing
pubs.organisational-group Pathology
pubs.organisational-group Physics
pubs.organisational-group Sanford School of Public Policy
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group Social Science Research Institute
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group Trinity College of Arts & Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 128
dc.identifier.eissn 1573-7217


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