Study provides insight into the progression and invasiveness of ductal breast cancer
Despite an enormous degree of intercellular heterogeneity in both ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), recurrent patterns of genomic imbalances determine the evolution from noninvasive to invasive disease in most cases. DCIS is a precursor lesion for invasive breast cancer if untreated, and it is found in about 45% of patients with IDC.
The 5-year survival for DCIS, when not accompanied by invasive disease, is nearly 100%, while it is 89% for all stage of invasive breast cancer and 24% for patients with distant metastasis.
This study was based on archived clinical samples where the co-occurrence of DCIS and IDC in the same patient had been tracked at the National Naval Medical Center. The genetic makeup of individual cells from 13 patients with DCIS and IDC was compared, and the gain or loss of specific genes frequently affected in DCIS and IDC were analyzed.
The researchers observed a high degree of chromosomal instability from one cell to another, since identical signal clones were only present in less than 20% of the cells. Despite the instability, most cases had a distribution of gains and losses that was consistent with known genetic aberration profiles for breast cancer. Patterns were consistent with nonrandom distribution of genetic imbalances. The strong oncogene MYC was most frequently gained from DCIS to IDC, so MYC appears to have a major role in the transition from in situ to invasive breast disease.
“For patients with cancer, the transition from locally controlled disease to a disseminated stage and metastases is probably the most critical threshold, because that transition makes surgical intervention considerably less likely to succeed,” said lead investigator Thomas Ried, MD, of the National Cancer Institute in Bethesda, Maryland. He explained, “This of course raises the question of what precisely determines this critical transition between preinvasive and invasive disease. Identifying the differences in the full catalog of genes in DCIS and IDC could have the potential of identifying a gene expression signature that is ultimately responsible for invasion and progression.”This research was published in The American Journal of Pathology (2012;181(5):1807-1822).