Prognostic and Predictive Value of HER2 Expression in Ductal Carcinoma In Situ: Results from the UK/ANZ DCIS Randomized Trial.

Purpose: HER2 is overexpressed more frequently in ductal carcinoma in situ (DCIS) than in invasive breast cancer but its prognostic significance and predictive role for radiotherapy has not been clearly established. We investigated the prognostic and predictive value of HER2 overexpression in DCIS. Experimental Design: HER2 expression was evaluated by IHC using the HercepTest™ in samples from UK/ANZ DCIS trial participants (n = 755) with IHC 3+ expression categorized as HER2 positive for primary analyses. Sensitivity analyses included HER2 categorization as negative (IHC 0,1+), equivocal (IHC 2+), and positive (IHC 3+) and analyses restricted to a nested case–control component where 181 cases (with recurrence) were matched to 362 controls by treatment arm and age. Results: Two-hundred and forty-five (34.4%) of evaluable 713 samples [181 ipsilateral breast events (IBE)] were HER2 positive. HER2 overexpression was associated with significantly increased risk of IBE [HR = 2.29; 95% confidence interval (95% CI), 1.64–3.14; P Conclusions: HER2 overexpression is associated with significantly increased risk of in situ recurrence and is also predictive of radiotherapy benefit, with greater reductions in in situ but not invasive recurrences in HER2-positive DCIS.