Abstract Background: Real-world data on treatment patterns and prevalence of brain metastases in patients with HER2+ metastatic breast cancer (mBC) are limited. This study described treatment patterns and clinical outcomes among patients with HER2+ mBC in Canada. Methods: This was a retrospective chart review of adult patients diagnosed with de-novo or recurrent HER2+ mBC between Jan 1, 2014 and Mar 1, 2021 (prior to wide availability of new treatments) at Sunnybrook Research Institute and Sinai Health, two large BC treatment centres in Canada. Data on patient characteristics and treatment regimens were extracted. Treatment patterns, time to next treatment (TTNT; as a proxy for progression-free survival), and presence of brain metastases were assessed in the first-line (1L), second-line (2L), and third-line (3L) settings. TTNT analyses used Kaplan-Meier methodology to account for censoring. Results: Of 121 patients with HER2+ mBC, the median (IQR) age was 54.0 (17.0) years. 38.0% of patients had de-novo disease and 62.0% had recurrent mBC; 12 (9.9%) had brain metastases at the time of mBC diagnosis. Systemic therapies generally aligned with Canadian funded regimens for 1L (101 of 121 patients [83.5%] received trastuzumab + pertuzumab ± chemotherapy ± subsequent endocrine therapy; 8/121 [6.6%] received endocrine therapy only) and 2L (50/68 [73.5%] received T-DM1 ± endocrine therapy; 9/68 [13.2%] received endocrine therapy only). However, treatment patterns were heterogeneous in the 3L setting (14/46 [30.4%] received anti-HER2 TKI + chemotherapy ± trastuzumab; 10/46 [21.7%] received endocrine therapy only; 10/46 [21.7%] received chemotherapy). Median (95% CI) TTNT in months was 21.4 (16.1, 27.2) in 1L, 11.0 (8.5, 16.5) in 2L, and 8.7 (5.4, 15.6) in 3L. Median (IQR) follow-up was 29.9 (25.2) months. In total, 57 patients (47.1%) were diagnosed with brain metastases during the study period (17 pre-1L, 24 post-1L/pre-2L, 6 post-2L/pre-3L) and of these, 73.7% received radiation therapy. Conclusions: In patients with HER2+ mBC in Canada, 3L treatment patterns are heterogeneous, median TTNT is <1 year, and almost half develop brain metastases. These data from two large treating centres in Ontario suggest a high unmet need for more effective treatment regimens in later lines of therapy, particularly 3L, for patients with HER2+ mBC. Citation Format: Katarzyna J Jerzak, Ruth Moulson, Ling-I Hsu, Chris Lenhu, Dhivo Krishnathasan, Jessica Weiss, Christine Brezden-Masley. Real-world treatment patterns and clinical outcomes in patients with HER2+ metastatic breast cancer receiving systemic therapy in Ontario, Canada [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A081.