Prognostic Value of ER and PgR Expression and the Impact of Multi-clonal Expression for Recurrence in Ductal Carcinoma

PURPOSE: The prognostic value of ER/PgR expression in ductal carcinoma in situ (DCIS) is unclear. We observed multi-clonality when evaluating ER/PgR expression in the UK/ANZ DCIS trial, therefore, we investigated the prognostic role of both uni-clonal and multi-clonal ER/PgR expression in DCIS. EXPERIMENTAL DESIGN: Formalin-fixed paraffin embedded (FFPE) tissues were collected from UK/ANZ DCIS trial participants (n=755) and ER/PgR expression was evaluated by immunohistochemistry in 181 cases (with recurrence) matched to 362 controls by treatment-arm and age. Assays were scored by the Allred method and by a newly devised clonal method - analyses categorising multi-clonal DCIS as ER/PgR-positive as per current practice (Standard) and as ER/PgR-negative (clonal) were performed. RESULTS: ER expression was multi-clonal in 11% (39/356) of ER-positive (70.6%, 356/504) patients. Ipsilateral breast event (IBE) risk was similarly higher in ER-multi-clonal and ER-negative DCIS as compared to DCIS with uni-clonal ER expression. ER-negative DCIS (clonal) had a higher risk of in situ IBE (DCIS-IBE) [Odds ratio (OR) 4.99; 95% Confidence Interval (CI) 2.66-9.36; p