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

Cowell, Catherine F., Weigelt, Britta, Sakr, Rita A., Ng, Charlotte K. Y., Hicks, James, King, Tari A., Reis-Filho, Jorge S. (July 2013) Progression from ductal carcinoma in situ to invasive breast cancer: Revisited. Molecular Oncology. ISSN 1574-7891

DOI: 10.1016/j.molonc.2013.07.005


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.

Item Type: Paper
Uncontrolled Keywords: Breast cancer Intraductal Intra-tumor genetic heterogeneity Darwinian evolution Genomics
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > cancer types > breast cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Hicks lab
Depositing User: Matt Covey
Date: 11 July 2013
Date Deposited: 19 Jul 2013 14:21
Last Modified: 19 Jul 2021 13:33
PMCID: PMC5528459
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