In fact, although a preliminary report implied that p16INK4a/RB is abnormally expressed in breast cancer [33], recent studies demonstrated that over-expression of p16INK4a is indicative of a more undifferentiated malignant phenotype in mammary carcinoma, such as the basal-like phenotype, in which ERα is generally negative [34]. This evidence concerns the gene ESR1 and breast carcinoma.