Does the Expression of Ki-67, p16 and COX-2 at Initial Diagnosis of Breast Atypia or Usual Ductal Hyperplasia Predict a Second Clinically Significant Event?

Abstract

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response enzyme COX-2) predicted risk of progression for ~50% of women diagnosed with ductal carcinoma in situ and treated by lumpectomy alone.