The pre-clinical experiments were paralleled by the conduct of a large, multicentric, retrospective observational study, i.e., the SePHER study, Administration Sequence in Pertuzumab-pretreated HER2 + ABC patients, aimed to explore the efficacy of T-DM1 in light of prior trastuzumab/pertuzumab treatment in the real-world setting. This evidence concerns the gene ERBB2 and aneurysmal bone cyst.