Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), and low-nuclear grade ductal carcinoma in situ (DCIS). The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low-nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations—most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression