Purpose: Few data are currently available regarding the efficacy and safety of T-DM1 in breast cancer (BC) patients with brain metastases (BM), since clinical trials excluded these patients or included highly selected ones. We report here the experience of our institutions with the T-DM1 use in daily care practice BM BC patients. Patients and methods: HER2+ BC patients presenting with BM treated by T-DM1 in one of our institutions, using a standard dose of 3.6 mg per kilogram intravenously every 21 days, were considered in this retrospective study. Dose delays, reductions, and discontinuations due to toxic effects were performed according to the product guidelines. Treatment was continued until progression or unacceptable toxicity. We analyzed efficacy data by recording tumor response rates, progression-free survival (PFS) and overall survival (OS), treatment compliance (Relative Dose Intensity [RDI]) and safety by analyzing clinical and biological toxicities using NCI CTCAE v4.03. Results: 17 patients were treated between 2012 and 2015, with a median age of 52.8 years (range 35.2-68.8 years). 81.3% of the tumors were of the invasive ductal carcinoma subtype. No tumor was recorded to be Scarf, Bloom and Richardson grade I, 47.1% were estrogen receptor negative. 94% of the patients presented with concomitant extra-cerebral disease, mainly bone (71%), liver (47%), lymph node (47%) and lung (12%) metastases. The number of previous chemotherapy and trastuzumab regimens in the metastatic setting were 3 (1-7) and 2 (1-7) respectively. 15 out of the 17 patients previously received the capecitabine – lapatinib association. All patients previously received a locoregional treatment for their BM (whole brain radiation therapy in 88.2% of the cases). After a median follow-up of 4.3 months (95%IC 3.5 – 13.6), 9 patients presented a disease progression (first site of progression: brain 5; meningeal 2; outside of the CNS 2), 4 patients died due to progressive disease and 13 patients are still alive. The median number of T-DM1 cycles was 6 (range 1-27). There were 5 partial responses (29.4%), with an additional 35.3% disease stabilization, for a total 64.7% of patients with clinical benefit. Median PFS was 5.5 months (95%CI: 2 – Not Reached). Median OS was not reached at the moment of the present statistical analysis. There were no presumed treatment-related deaths. No dose reduction was required, the median RDI was 1. Treatment was well tolerated, without unexpected toxicities, treatment delay or dose reduction. Only one patient discontinued T-DM1 after 27 cycles due to bilirubin increase, while experiencing sustained disease stability. There were only one grade 3 toxicity (fatigue), and no reported grade 4 toxicities. Conclusion: In this limited population of unselected, heavily pretreated, patients affected by BM from HER2+ BC, T-DM1 appears to be a safe option, with clinical activity, even if it appears inferior to the ones reported in the pivotal trials. These results could be linked to the more advanced status of the population. A larger population, altogether with a longer follow-up appears mandatory to more accurately evaluate this agent in the BC BM. Thus this study will be updated for the meeting in term of number of patients and follow-up. Citation Format: Jacot W, Pons E, Guiu S, Levy C, Frenel J-S, Bachelot T, D9Hondt V, Firmin N, Romieu G, Thezenas S, Dalenc F. Trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer and brain metastases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-03.