Purpose: To assess telomere DNA content (TC) and the number of sites of allelic imbalance (AI) as a function of breast cancer progression.
Experimental design: TC and AI were determined in 54 histologically normal tissues, 10 atypical ductal hyperplasias (ADH), 122 in situ ductal carcinomas (DCIS) and 535 invasive carcinomas (Stage I-IIIA).
Results: TC was altered in ADH lesions (20%), DCIS specimens (53%) and invasive carcinomas (51%). The mean number of sites of AI was 0.26 in histologically normal group tissue, increased to 1.00 in ADH, 2.94 in DCIS, and 3.07 in invasive carcinomas. All groups were statistically different from the histologically normal group (P < 0.001 for each); however, there was no difference between DCIS and the invasive groups.
Conclusions: Genomic instability increases in ADH and plateaus in DCIS without further increase in the invasive carcinomas, supporting the notion that invasive carcinomas evolve from or in parallel with DCIS.