Untreated Ductal Carcinoma In Situ is Likely to Become Invasive Breast Cancer, Genetics Suggest
“Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum,” reported Kerstin Heselmeyer-Haddad, PhD, and colleagues from the National Cancer Institute and the National Center for Biotechnology Information, in Bethesda, Maryland, and Carnagie Mellon University's Department of Biological Sciences in Pittsburgh, Pennsylvania.
“From a clinical point of view, the high degree of chromosomal instability and the advanced aberration profile of DCIS make it unlikely that progression to invasive disease can be prevented with measures other than surgery and radiation,” the authors concluded.
The authors inferred that some DCIS cells are already “equipped” with genomic aberrations that allow metastasis.
Using single DCIS and IDC cells from stored samples representing 13 patients who had both DCIS and breast cancer, the researchers studied copy number changes for the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor-suppressor genes DBC2, CDH1, and TP53.
DCIS cells exhibited less chromosomal instability than IDC cells, the authors reported. Identical signal clones were found in <20% of cells, the authors noted.
“Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances,” they wrote. “CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC.”
In four cases, DCIS cells exhibited “identical clonal imbalances” to those found in IDC cells. In six cases, genomic switches occurred during transition from DCIS to IDC, in four of which a gain of MYC copy number was noted, the authors reported. MYC is a an oncogene involved in cellular proliferation, growth and differentiation, and is believed to play an important role in the transition of DCIS to IDC.
In approximately 45% of patients diagnosed with invasive ductal carcinoma, DCIS is also present.