Background: BM in HER2-positive BC patients are increasing, without agreement on the appropriate treatment of this subgroup. The disrupted blood-brain barrier in the setting of BM may allow the penetrance of T-DM1, with little evidence of its efficacy in this situation. Methods: HER2-positive BC patients treated with T-DM1 monotherapy at Ramon y Cajal Hospital (Madrid) from 2012 to 2017 were eligible. We differentiated patients without BM, stable BM (those with BM who had received local treatment for them and they were not in progression) and progressive BM (those who were in brain progression to a local treatment) at the beginning of T-DM1. We collected hormone receptors (HR) status, neoadjuvant treatment, number of previous treatments for metastatic BC, patients who received taxanes, pertuzumab or both, sites of metastatic disease, duration of T-DM1 and sites of progression. We analysed progression free survival (PFS) in total population and in both subgroups (patients with or without BM). Results: We identified 29 patients, 69% had positive HR, 45% had received neoadjuvant treatment and 55% had received 2 or more prior lines of treatment. Of total, 97% received taxanes and 38% received pertuzumab. Most patients had visceral disease. Patients received a median of 5 cycles of T-DM1, median duration of T-DM1 was 13 weeks and 4 remain on treatment at time of analysis. Before starting T-DM1, 28% had known BM (75% stable, the rest in progression). Only 10% of patients had cerebral progression during T-DM1. 19 patients had systemic progression during T-DM1, 2 of them with brain progression at same time, and 9 patients presented brain progression after finishing T-DM1. Median PFS was 21 months (m) in total population (confidence interval [CI] 95%: 12,58-28,94), 5 m in patients with BM (CI 95%: 3,88-6,50) and 24 m in those patients without BM when T-DM1 was started (CI 95%: 12,58-28,94). T-DM1 showed benefit in terms of PFS in patients without BM at the beginning of treatment in comparison with those with baseline BM (HR 0,297, p = 0,014). Conclusions: T-DM1 seems to be an effective therapeutic option in unselected HER2-positive BC patients with BM, but these findings require a prospective validation. Legal entity responsible for the study: Elena López Miranda, Roberto Martín Huertas. Funding: Roche Pharma. Disclosure: All authors have declared no conflicts of interest.