Cluster-4 samples were significantly associated with high nuclear grade, HER2 amplification, negative ERα status, negative PR status, and non-luminal intrinsic subtype (P = 0.038, P = 0.018, P <0.001, P = 0.001, and P <0.001, respectively) compared with DCIS samples in the other clusters (Additional file 6). This evidence concerns the gene ESR1 and ductal breast carcinoma in situ.