In this context, a robust association has been found between ER-positvie status and other prognostic factors including lower nuclear grade, smaller tumor size, HER2-negative status, and the absence of comedo necrosis.293 Notably, ER expression is higher in low-grade DCIS but lower in high-grade DCIS.14 This evidence concerns the gene ESR1 and ductal breast carcinoma in situ.