Background: Trastuzumab is well known to be effective to control locoregional recurrence and distant metastasis of human epidermal growth factor receptor 2 (HER2)-overexpressing breast tumor. However, few studies have reported the effect of ipsilateral breast tumor recurrence (IBTR) in spite of higher incidence of IBTR for HER2 overexpressing subtype than other subtypes. The purpose of this study is to investigate the difference in the incidence of IBTR of HER2-overexpressing breast tumor according to adjuvant trastuzumab. Methods: We retrospectively reviewed 996 patients who had done surgery for HER2-overexpressing breast cancer between January 2000 and December 2017 in our institution. Patients with tumors smaller than 0.5cm without axillar node metastasis were excluded. As regarding IBTR as recurrence “in” the ipsilateral breast, only patients who had done breast conserving surgery were included. Results: There were 735 patients who had finished adjuvant trastuzumab as first planned and 555 patients with hormone receptor positive. Median follow-up period for all patients was 70.7 months (range 12.7-239.6 months). The 10-year IBTR-free survival rate showed a significant benefit for the group treatment with trastuzumab than the group without trastuzumab (97.0% versus 91.9%; p=0.007). In a multivariate analysis, presence of lymphovascular invasion (Hazard ratio [HR], 2.53; 95% Confidence interval [CI], 1.19 - 5.41), closed or involved resection margin (HR, 2.62; 95% CI, 1.20 - 5.74), positive hormone receptor (HR, 3.70; 95% CI, 1.69 - 8.08), positive axillar lymph node (HR, 5.21; 95% CI, 1.75 - 15.57), and omitted or uncompleted adjuvant trastuzumab (HR, 2.72; 95% CI, 1.11 - 6.67) were independent predictors of IBTR. However, subgroup analysis of the patients with hormone receptor negative tumor showed no benefit of adjuvant trastuzumab (98.1% versus 96.6%, p=0.669) while it controlled IBTR for hormone receptor positive tumor (95.7% versus 86.2%; p=0.002). When additionally analzyed, trastuzumab showed benefit for 10-year locoregional recurrence-free survival (95.5% versus 89.7%, p=0.012) and distant metastasis-free survival (93.5% versus 77.8%, pConclusions: Trastuzumab has a clinical benefit in not only locoregional recurrence but also IBTR among HER2-overexpression breast cancer, especially with negative hormone receptor. Citation Format: Jong Ho Cheun, Han-Byoel Lee, Hyeong-Gon Moon, Dong-Young Noh, Wonshink Han. Impact of trastuzumab on Ipsilateral breast tumor recurrence after breast conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-13.