However a phase I study in advanced breast carcinoma with the combination of exemestane and tremelimumab has been recently reported, demonstrating that the combination is well tolerated and associated with an increased expression of inducible costimulator (ICOS+) in peripheral T CD4+ and CD8+ cells, which likely signals immune activation secondary to CTLA-4 blockade [68]. This evidence concerns the gene CTLA4 and breast carcinoma.