Abstract Purpose: The development of trastuzumab has significantly improved prognosis and treatment of Her2 positive breast cancer. The efficacy of trastuzumab monotherapy is limited and thus standard of care is to combine trastuzumab with chemotherapy. Yet for those who cannot tolerate chemotherapy, there is no randomized data comparing no trastuzumab with trastuzumab monotherapy in the non-metastatic setting. We therefore examined the outcomes of non-metastatic patients treated with trastuzumab without chemotherapy in the National Cancer Database (NCDB). Methods: We included female patients from 2013-2016 with clinical stage I-III breast cancer who received surgery with ER+/HER+ disease. Patients treated with Her2 therapy after 2013 had their treatment classified under immunotherapy, whereas those treated before 2013 had Her2 therapy classified under chemotherapy. Exclusion criteria included male sex, prior cancer history, and clinical stage IV disease. We also excluded patients with pathologic stage 0 (DCIS), stage IV, or unknown pathologic stage. Treatments compared included chemotherapy (CT), adjuvant hormone therapy alone (HT), combination HT + trastuzumab (HT+T), and no adjuvant treatment (NT). Pearson chi square analysis, one-way ANOVA, and the Kaplan Meier method was used to evaluate the differences in clinical characteristics for the treatment groups and effects of treatment on overall survival. Results: We identified 46,025 patients who met eligibility criteria. The median follow-up was 31 months (SD 13.16) for CT, 30 months (SD 14.07) for HT, 30 months (SD 12.87) for HT + T, and 27 months (SD 14.61) for NT. Most patients received standard of care with CT (78%, n=36008), 12% (n=5632) received adjuvant HT without T (HT), 3% (n=1157) were treated with HT+T, and 12% (n=2669) with NT. There was a higher representation of elderly patients >70 years old in the HT (41%) and HT +T (51%) and NT arm (38%) compared to the CT arm (13%). There was a higher representation of lobular histology specifically in the HT + T arm (52%) compared to CT (11%), HT (11%), or NT arm (11%). There was a higher representation of patients with Charlson Deyo Comorbidity Scores of 1-2 (vs. 0) in the HT (21%) and HT +T arms (21%) compared to the CT (15%) or NT (18%) arms. There was a higher representation of node positive patients (N1-3 vs. N0) in the CT (38%) and HT+T (27%) groups vs. the HT (13%) and NT (16%) arms. Similarly, there were more patients with high grade disease (G3) and lymphovascular invasion (+LVI) in the CT (48% G3, 25% +LVI) and HT+T (45% G3, 20% +LVI) arms vs. in the HT (30% G3, 12% +LVI) and NT (39% G3, 15% +LVI) arms. Medicare patients were more likely to be treated with HT +T (58%) or HT (50%) than CT (24%) or NT (45%) which likely reflects the overlap of Medicare and older age. As compared to the standard of care CT arm, the patients treated without CT, had significantly worse overall survival. There was no improvement in OS for HT+T vs. HT without T. Hazard ratios for treatment regimens without CT were significantly worse with a HR 2.26 (95% CI 0.4-1.9) for HT without T, 3.01 (95% CI 0.3-2.3) for HT + T, and 4.37 (95% CI 3.7-5.1) for NT (p<0.0001). Conclusions: This is the largest retrospective analysis of US patients with ER+/HER2+ non-metastatic breast cancer. Those treated with HT + T (vs. CT, HT, and NT) are more likely to have lobular histology. Patients treated with HT+T (vs. HT) are more likely to have more aggressive disease including higher nodal stage, higher grade, and the presence of LVI. Those treated with HT+T (vs. CT) are more likely to be older. We fail to identify an OS benefit with HT + T compared to HT alone though further analysis including a multivariate analysis and propensity score matching will further elucidate the outcome of this group. Citation Format: Susanna Nguy, S. Peter Wu, Cheongeun Oh, Naamit K Gerber. Outcomes of patients with ER+/HER2+ non-metastatic breast cancer treated with trastuzumab without chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-02.