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An interesting article by Kerlikowske et al. (1) in this issue of the Journal describes how certain biomarkers in ductal carcinoma in situ (DCIS) treated with lumpectomy alone may improve our ability to predict the risk of disease recurrence and progression to invasive breast cancer (IBC). Once DCIS is detected, this therapeutic setting reflects the natural history of any residual disease, and the likelihood of regrowth and progression largely determines the use of adjuvant therapy. The tumor samples used in this retrospective study were a case – control subset nested within a cohort of nearly 1200 patients who were diagnosed with DCIS between 1983 and 1994 and for whom long-term clinical follow-up data were available. In assembling samples from this cohort, the investigators have created a rare and valuable resource, and they have used it in previous enlightening studies of DCIS published in this Journal (2) and elsewhere (3). Cases of primary DCIS in the study population with available glass slides (n = 502) were comprehensively evaluated for standard his-topathologic features, including tumor size, nuclear grade, and status of surgical margins. A subset of the reviewed cases with available paraffi n blocks (n = 329) were further evaluated by immu-nohistochemistry for expression of several biomarkers. Many of the biomarkers are well known in this setting, including the estro-gen receptor (ER), progesterone receptor, p53, human epidermal growth factor receptor 2 (ERBB2, also known as HER2), and Ki67, whereas others are relatively novel, including p16 and cyclooxygenase-2 (COX-2). All of these factors, and available clinical characteristics, were evaluated individually for their univariate associations (hazard ratio [HR]) with recurrence of DCIS or progression to IBC, with a median follow-up of about 8 years. Larger tumor size, positive surgical margins, and higher nuclear grade were each associated with modestly increased risks for recurrent DCIS (HR = 1.4 to 3.6) and IBC (HR = 1.2 to 1.6), although the latter were not statistically signifi cant. The same histopathologic features were strongly related to recurrences of both DCIS and IBC in a study involving many of the same patients that was published by these investigators 7 years ago (2). The reasons for this apparent loss of predictive ability are unclear, but at least one other study has reported weakened associations between histopathologic features and recurrence with prolonged follow-up (4), suggesting that these features are more predictive of the rate than the fate of tumor progression (5). …

Biomarkers Predicting Recurrence and Progression of Ductal Carcinoma In Situ Treated by Lumpectomy Alone