Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women

BACKGROUND. Patients diagnosed with ductal carcinoma in situ (DCIS) at a young age appear to have a different natural history and biology, including a higher local relapse rate, than patients diagnosed later in life. The current study compared various pathologic and molecular features of DCIS arising in a cohort of young women with those of DCIS arising in a cohort of older women to identify potential biologic differences between these two populations of patients. METHODS. The study population consisted of 20 patients age <42 years and 34 patients age > 60 years who were treated at Yale University School of Medicine with breast-conserving therapy (BCT) and whose archival paraffin blocks were available and had sufficient tumor for staining. The original slides from each case were reviewed and the most representative specimen block from each case was processed for immunohistochemical staining. Pathologic characteristics evaluated for each case included histology, grade, and presence of necrosis. Paraffin-embedded sections were immunohistochemically evaluated for expression of HER-2/neu, estrogen receptor (ER), progesterone receptor (PR), bcl-2, cyclin D1, Ki-67, and p53. RESULTS. Although there was no difference in pathologic features of the tumors between the two groups, HER-2/neu was found to be overexpressed in a greater percentage of the younger population (P = 0.06). There was no apparent difference in expression of the other markers. Of note, HER-2/neu expression was correlated with high nuclear grade (P = 0.004), necrosis (P = 0.06), and ER and PR negativity (P = 0.01 and P = 0.03, respectively) in the combined population. CONCLUSIONS. The current study data suggested that HER-2/neu overexpression in younger patients may characterize a biologic difference in their tumor and may partially contribute to their higher risk of recurrence. Further studies are needed to assess whether this difference holds independent of grade and to evaluate the prognostic significance of HER-2/neu overexpression in DCIS.