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Uniform TitleEvaluation of pathways for progression of heterogeneous breast tumors
PublisherElsevier
NameAxelrod, David E. (author), Sontag, Laura (author), New Jersey Commission on Cancer Research,
Date Created2005
SubjectBreast cancer,
Tumor progression,
Invasive ductal carcinoma,
Breast ductal carcinoma in situ,
Breast--Cancer,
Cancer invasiveness
DescriptionTo better understand the progression of heterogeneous breast cancers, four models of progression pathways have been evaluated.
The models describe the progression through the grades of ductal carcinoma in situ (DCIS) 1, 2, and 3, and through the grades of
invasive ductal carcinoma (IDC) 1, 2, and 3. The first three pathways, termed linear, nonlinear, and branched, describe DCIS as a
progenitor of IDC, and grades of DCIS progressing into grades of IDC. The fourth pathway, termed parallel, describes DCIS and
IDC as diverging from a common progenitor and progressing through grades in parallel. The best transition rates for the linear,
nonlinear, and branched pathways were sought using a random search in combination with a directed search based on the
Nelder–Mead simplex method. Parameter values for the parallel pathway were determined with heuristic graphs. Results of
computer simulation were compared with clinically observed frequencies of grades of DCIS and grades of IDC that were reported to
occur together in heterogeneous tumors. Each of the four pathways could simulate frequencies that resembled, to varying degrees,
the clinical observations. The parallel pathway produced the best correspondence with clinical observations. These results quantify
the traditional descriptions in which grades of DCIS are the progenitors of grades of IDC. The results also raise the alternative
possibility that, in some tumors with both components, DCIS and IDC may have diverged from a common progenitor.
The models describe the progression through the grades of ductal carcinoma in situ (DCIS) 1, 2, and 3, and through the grades of
invasive ductal carcinoma (IDC) 1, 2, and 3. The first three pathways, termed linear, nonlinear, and branched, describe DCIS as a
progenitor of IDC, and grades of DCIS progressing into grades of IDC. The fourth pathway, termed parallel, describes DCIS and
IDC as diverging from a common progenitor and progressing through grades in parallel. The best transition rates for the linear,
nonlinear, and branched pathways were sought using a random search in combination with a directed search based on the
Nelder–Mead simplex method. Parameter values for the parallel pathway were determined with heuristic graphs. Results of
computer simulation were compared with clinically observed frequencies of grades of DCIS and grades of IDC that were reported to
occur together in heterogeneous tumors. Each of the four pathways could simulate frequencies that resembled, to varying degrees,
the clinical observations. The parallel pathway produced the best correspondence with clinical observations. These results quantify
the traditional descriptions in which grades of DCIS are the progenitors of grades of IDC. The results also raise the alternative
possibility that, in some tumors with both components, DCIS and IDC may have diverged from a common progenitor.
NoteThe published version of this article is available at: http://www.elsevier.com/locate/yjtbi
NoteJournal title: Journal of Theoretical Biology; volume: 232; date: 2005;
Notedoi:10.1016/j.jtbi.2004.08.002
Genrearticles
Persistent URLhttp://hdl.rutgers.edu/1782.2/rucore30017800001.Article.17038
LanguageEnglish
CollectionAxelrod David Collection
Organization NameRutgers, The State University of New Jersey
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