Open AccessProgression from ductal carcinoma in situ to invasive breast cancer: Revisited
Author(s) -
Cowell Catherine F.,
Weigelt Britta,
Sakr Rita A.,
Ng Charlotte K.Y.,
Hicks James,
King Tari A.,
Reis-Filho Jorge S.
Publication year - 2013
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2013.07.005
Subject(s) - ductal carcinoma , breast cancer , biology , myoepithelial cell , carcinoma in situ , genetic heterogeneity , stroma , cancer research , cancer , tumor progression , carcinoma , pathology , tumor microenvironment , oncology , phenotype , medicine , immunology , genetics , gene , immunohistochemistry
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.