Abstract Background. Clinical trials have demonstrated an increased risk of cancer treatment related cardiac dysfunction (CTCD) during trastuzumab(H) therapy. Diabetes, dyslipidemia, and obesity are also known risk factors for cardiovascular disease. The primary objective of this study was to evaluate the incidence of asymptomatic drop in left ventricular ejection fraction (AD-LVEF) and symptomatic CTCD (S-CTCD) in women with BC and co-morbidities receiving H, referred to a dedicated cardio-oncology clinic (COC). Methods. This was a retrospective cohort study of women with BC (all stages) referred to The Ottawa Hospital COC between 2008 and 2015, who received chemotherapy (CT) and H. Data collected included: demographics, reason for referral, cardiac testing (MUGA/ECHO) co-morbidities (diabetes, dyslipidemia) and cardiac outcomes. Obesity defined as body mass index > 30. Symptomatic CTCD include SOB, PND, orthopnea, peripheral edema, congestive heart failure. Asymptomatic drop in LVEF defined as decrease of at least 15% from baseline; normal LVEF, or a decrease of at least 10% in LVEF, less than 53%. Results. Chemotherapy (A-CT) followed by H, 62 received H without A-CT. 139 patients with no history diabetes, dyslipidemia, or obesity, referred with AD-LVEF (68%), with S- CTCD (30%), pre-CT assessment (2%). Obesity (O) pre-existing co-morbidity in 63 (26%) patients, (20 (32%) with S-CTCD, 40 (63%) referred with AD-LVEF, 3(5%) referred for pre-CT assessment). Dyslipidemia (L) – 52 (21%); referred with S-CTCD 15; 29%), with AD-LVEF 31 (60%), pre-CT assessment 6 (11). Diabetes (D) – 29 (12%) - (6 (21%) with S-CTCD, 19 (66%) referred with AD-LVEF, 4(13%) referred for pre-CT assessment). Combination of two or three conditions significantly increase incidence of S-CTCD: O+L – 67%, O+D – 69%, O+L+D – 72%. Combination of obesity and other conditions significantly increase incidence of S-CTCD: O+L – 67%(Relative Risk -2.2, p=0,04), O+D – 69% (RR-2.3, p=0,02), O+L+D – 72% (RR-2.4, p=0,08). Conclusion. The combination of two or three co-morbidities significantly increases the incidence of S-CTCD. BC patients experiencing CTCD with pre-existing history of diabetes, dyslipidemia, and obesity may require more proactive strategies for prevention, detection and treatment of cardiotoxicity during trastuzumab-based treatment. Citation Format: Aseyev O, Johnson C, Turek M, Stadnick E, Law A, Gosh N, Dent S. Obesity, dyslipidemia, and diabetes as risk factors for trastuzumab-related cardiotoxicity in breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-06.