Background: The treatment of Human Epidermal Growth Factor -2 (HER2) positive breast cancer has advanced since Trastuzumab and subsequently Pertuzumab were introduced and approved as antibody-targeted therapy. With the incorporation of anti-HER2 therapy, cardiotoxicity poses a significant risk and is a well know side effect. This toxicity can increase with concomitant use of Anthracyclines. Left Ventricular Global Longitudinal Strain is assessed using speckle tracking analysis on 2D echocardiogram and a relative reduction in LV global longitudinal strain (GLS) of 10-15% from baseline appears to have specificity to predict downstream reduction in Left Ventricular Ejection Fraction (LVEF). There is growing use for identification of GLS changes in these patients and its incorporation into medical decision making that impacts oncological and cardiac care. Methods: We conducted an analysis of 200 patients receiving anti-HER2 therapy at Henry Ford Cancer institute from Jan 1, 2016 to June 1, 2022 to determine if there was a 10-15% reduction in GLS detected prior to a decrease in ejection fraction and if and how these detections resulted in the implementation of cardio protective measures and downstream effects on cancer therapy. Results: There were 198 patients with GLS and LVEF data. 175 patients (88.3%) completed one year of cancer therapy 107/198 patients (54%) had no change in GLS or LVEF. 91/198 patients (45%) had changes in GLS and or LVEF. 41/91 (45%) patients with LVEF decline did not have cardioprotective intervention implemented. Despite this, 34 (83%) of these patients completed cancer treatment. 50/91 (55%) patients did have cardioprotective interventions with 40 (78%) patients from this subgroup completing cancer treatment. 81% of patients with EF decline were able to complete treatment. 50% of patients with EF decline had EF recovery within 6 months of completion of cancer therapy. The odds of LVEF decline were 9.8 times higher for those with GLS decline (OR=9.0, p< 0.001). Patients with LVEF decline were more likely to have cardio preventive intervention (OR=18.8, p< 0.001). Multivariate analysis did not find an association between cardiac risk factors such as hypertension, diabetes mellitus, smoking, obesity and hyperlipidemia with GLS decline. There was no disparity by race. Conclusion: Our study revealed that early changes in GLS and LVEF did not impact the completion of cancer treatment irrespective of implementation of cardioprotective measures. Citation Format: Hussna E. Abunafeesa, Cortney Mckay, Pin Li, Madhulata Reddy, Vrushali Dabak. Changes in Left Ventricular Global Longitudinal Strain in breast cancer patients receiving anti-HER2 and/or Adriamycin therapy and outcomes with early implementation of cardio-protective measures [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-35.