Background: Central nervous system (CNS) metastases are frequent in Her2 positive breast cancers (BC). Local treatment remains the standard of care, however systemic treatments may also represent a therapeutic option. Ado-trastuzumab Emtansine (TDM1) significantly improves outcomes of Her2 positive BC patients (pts), but only a few data have been published on its impact on CNS metastases. This multicentric retrospective cohort aims to evaluate the efficacy/safety of TDM1 in this setting in the common practice. Methods: Data from 14 pts treated with TDM1 for CNS metastases of Her2 positive breast cancers since February 2013 were retrospectively collected in two sites. RANO criteria were used for the CNS evaluation and RECIST criteria for systemic evaluation, both performed every 9 weeks. Safety was evaluated according to the NCI-CTC criteria. Results: Median age was 48.6 years (34.4-63.5). Median follow up was 12 months (mos) (5.4-35.9). Tumours were CCI (13/14) or CLI (1/14) and 10 (71%) expressed hormone receptors. Pts had brain metastases in 10 cases, leptomeningeal metastases in 1 and both in 3. Median number of previous chemotherapy regimens was 2 (0-7). Pts had received a prior treatment with trastuzumab in 13 cases, lapatinib in 11, pertuzumab in 1. TDM1 was administered as first treatment of CNS metastases in 1 case, and for progressive CNS metastases in 13. The median number of TDM1 cycles was 4 (1-13). CNS responses were achieved in 4/14 cases (28%), CNS stabilization in 3/14 cases (21%) and the median CNS progression free survival was 2.43 mos (2-9.4). Systemic responses were observed in 3/11 (27%) while systemic stabilizations were noted in 5 (45%) pts. First sites of progression were systemic: 2 cases (15%), CNS: 7 (53%) or both 2 (15%). TDM1 was discontinued in 2 pts for toxicity. TDM1 is still ongoing for one pt. The median OS was 9.07 mos (3.65-24.8). Ten pts are still alive. Treatment was well tolerated with only 2 grade 3/4 adverse events (1 pancreatitis and 1 skin toxicity). Conclusions: TDM1 shows significant efficacy in this non-selected population according to RANO criteria. This study is still ongoing prospectively and results will be updated for the meeting.