Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences

Background: Ductal carcinoma in situ (DCIS) recurs in the same breast follo wing breast-conserving surgery in 5%-25% of patients, with the rate influen ced by the presence or absence of involved surgical margins, tumor size and nuclear grade, and whether or not radiation therapy was performed. A recur rent lesion arising soon after excision of an initial DCIS may reflect resi dual disease, whereas ill situ tumors arising after longer periods are some times considered to be second independent events. The purpose of this study was to determine the clonal relationship between initial DCIS lesions and their recurrences. Methods: Comparative genomic hybridization (CGH) was use d to compare chromosomal alterations in 18 initial DCIS lesions (presenting in the absence of invasive disease) and in their subsequent ipsilateral DC IS recurrences (detected from 16 months to 9.3 years later). Results: Of th e 18 tumor pairs, 17 showed a high concordance in their chromosomal alterat ions (median = 81%; range = 65%-100%), while one case showed no agreement b etween the paired samples (having two and 20 alterations, respectively). Mo rphologic characterization of the DCIS pairs showed clear similarities. The mean number of CGH changes was greater in the recurrent tumors than in the initial lesions (10.7 versus 8.8; P = .019), The most common changes in bo th the initial and the recurrent in situ lesions were gains involving chrom osome 17q and losses involving chromosomes 8p and 17p, The degree of concor dance was independent of the time interval before recurrence and of the pre sence of positive surgical margins. Conclusions: In this study, DCIS recurr ences were clonally related to their primary lesions in most cases. This fi nding is consistent with treatment paradigms requiring nide surgical margin s and/or postoperative radiation therapy.