Progression from ductal carcinoma in situ to invasive breast cancer: Revisited Journal Article


Authors: Cowell, C. F.; Weigelt, B.; Sakr, R. A.; Ng, C. K. Y.; Hicks, J.; King, T. A.; Reis-Filho, J. S.
Article Title: Progression from ductal carcinoma in situ to invasive breast cancer: Revisited
Abstract: Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that is separated from the breast stroma by an intact layer of basement membrane and myoepithelial cells. DCIS is a non-obligate precursor of invasive breast cancer, and up to 40% of these lesions progress to invasive disease if untreated. Currently, it is not possible to predict accurately which DCIS would be more likely to progress to invasive breast cancer as neither the significant drivers of the invasive transition have been identified, nor has the clinical utility of tests predicting the likelihood of progression been demonstrated. Although molecular studies have shown that qualitatively, synchronous DCIS and invasive breast cancers are remarkably similar, there is burgeoning evidence to demonstrate that intra-tumor genetic heterogeneity is observed in a subset of DCIS, and that the process of progression to invasive disease may constitute an 'evolutionary bottleneck', resulting in the selection of subsets of tumor cells with specific genetic and/or epigenetic aberrations. Here we review the clinical challenge posed by DCIS, the contribution of the microenvironment and genetic aberrations to the progression from in situ to invasive breast cancer, the emerging evidence of the impact of intra-tumor genetic heterogeneity on this process, and strategies to combat this heterogeneity. © 2013 Federation of European Biochemical Societies.
Keywords: unclassified drug; review; cancer growth; genetic analysis; breast cancer; epidermal growth factor receptor 2; cancer genetics; chromosome aberration; myc protein; membrane protein; genomics; intraductal carcinoma; fibroblast growth factor receptor 1; genetic heterogeneity; tumor microenvironment; intraductal; darwinian evolution; intra-tumor genetic heterogeneity; ccnd1 protein; invasive breast cancer
Journal Title: Molecular Oncology
Volume: 7
Issue: 5
ISSN: 1878-0261
Publisher: FEBS Press  
Date Published: 2013-10-01
Start Page: 859
End Page: 869
Language: English
DOI: 10.1016/j.molonc.2013.07.005
PROVIDER: scopus
PUBMED: 23890733
PMCID: PMC5528459
DOI/URL:
Notes: --- - "Export Date: 1 October 2013" - "Source: Scopus"
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MSK Authors
  1. Tari King
    186 King
  2. Rita Sakr
    61 Sakr
  3. Britta Weigelt
    632 Weigelt
  4. Kiu Yan Charlotte Ng
    155 Ng
  5. Catherine Frances Cowell
    10 Cowell