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JNCI Journal of the National Cancer Institute 2000 92(4):313-320; doi:10.1093/jnci/92.4.313
© 2000 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 92, No. 4, 313-320, February 16, 2000
© 2000 Oxford University Press

Chromosomal Alterations in Ductal Carcinomas In Situ and Their In Situ Recurrences

Frederic M. Waldman, Sandy DeVries, Karen L. Chew, Dan H. Moore II, Karla Kerlikowske, Britt-Marie Ljung

Affiliations of authors: F. M. Waldman, S. DeVries, K. L. Chew, D. H. Moore (Cancer Center), K. Kerlikowske (Department of Epidemiology and Biostatistics and General Internal Medicine Section, Department of Veterans Affairs), B.-M. Ljung (Department of Pathology), University of California, San Francisco.

Correspondence to: Frederic Waldman, M.D., Ph.D., Cancer Genetics Program, UCSF Cancer Center, Rm. S436, University of California, San Francisco, San Francisco, CA 94143 (e-mail: waldman{at}cc.ucsf.edu).

BACKGROUND: Ductal carcinoma in situ (DCIS) recurs in the same breast following breast-conserving surgery in 5%-25% of patients, with the rate influenced by the presence or absence of involved surgical margins, tumor size and nuclear grade, and whether or not radiation therapy was performed. A recurrent lesion arising soon after excision of an initial DCIS may reflect residual disease, whereas in situ tumors arising after longer periods are sometimes 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 used to compare chromosomal alterations in 18 initial DCIS lesions (presenting in the absence of invasive disease) and in their subsequent ipsilateral DCIS recurrences (detected from 16 months to 9.3 years later). RESULTS: Of the 18 tumor pairs, 17 showed a high concordance in their chromosomal alterations (median = 81%; range = 65%-100%), while one case showed no agreement between the paired samples (having two and 20 alterations, respectively). Morphologic 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 both the initial and the recurrent in situ lesions were gains involving chromosome 17q and losses involving chromosomes 8p and 17p. The degree of concordance was independent of the time interval before recurrence and of the presence of positive surgical margins. CONCLUSIONS: In this study, DCIS recurrences were clonally related to their primary lesions in most cases. This finding is consistent with treatment paradigms requiring wide surgical margins and/or postoperative radiation therapy.



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