Despite the lower prevalence of driver mutations in pure DCIS than synchronous DCIS-IDC, even pure DCIS with a low nuclear grade (case PD22) harbored at least one driver such as TP53, PIK3CA, AKT1, PTEN, GATA3 and PIK3R1 mutations, suggesting that these drivers may be essential for the early phase of DCIS development and that gradual accumulation of driver mutations might be required for progression. Here, PIK3CA is linked to ductal breast carcinoma in situ.