CLASSIFICATION OF DUCT CARCINOMA IN-SITU (DCIS) WITH A CHARACTERIZATION OF HIGH-GRADE LESIONS - DEFINING COHORTS FOR CHEMOPREVENTION TRIALS

In the last 6 years a number of non-randomized, predominantly single i nstitutional trials of breast conservation therapy (BCT) with DCIS, ha ve demonstrated that it constitutes a very heterogeneous group of dise ases with markedly different risks of local recurrence and invasive tr ansformation. There has been a consensus that DCIS, which exhibits a ' 'comedo'' morphology, generally defines a high risk group. Most studie s, moreover, have identified the same two features, nuclear grade and necrosis, as contributing most significantly to prognosis [4-6]. Nucle ar grade and necrosis have been identified as independent prognostic v ariables in several studies [5,6]. High nuclear grade DCIS which exhib its comedo necrosis defines the majority of all DCIS which will result in local recurrence and invasive transformation after BCT. Studies ut ilizing image cytometry, to determine ploidy and S-phase fraction and immunohistochemical studies of proliferation and oncogene distribution have shown a significant association with morphologically identified high nuclear grade and aneuploidy, high S-phase fraction or proliferat ion rate, presence of HER-2/neu and P53 oncogenes and absence of estro gen receptors. Generally the inverse of this association is seen with low nuclear grade DCIS. However, initial hopes that these adjunctive s tudies would identify subsets within the high nuclear grade group whic h might be more likely to recur have not been fulfilled. (C) 1997 Wile y-Liss, Inc.