Using IHC techniques, we investigated the phosphorylation of ER-α Ser118 and ER-α Ser167, and expression of ER-α, ER-β1, ER-βcx/β2, PR, PRA, and PRB, in primary breast tumor specimens from 75 patients with metastatic breast cancer who, on relapse, received endocrine therapy as first-line treatment. This evidence concerns the gene RB1 and breast neoplasm.