Abstract Purpose: The ATEMPT trial sought to determine if adjuvant T-DM1 (every 3 wks for 1 yr) for Stage I HER2 positive breast cancer is better tolerated than TH (paclitaxel weekly x 12 wks with 1 yr of trastuzumab). Here we compare patient-reported outcomes (PROs) including quality of life (QOL), specific symptoms, and work productivity between the two treatments over time. Patients and Methods: English-speaking patients were randomized (3:1) to T-DM1 or TH, and completed PRO assessments at baseline (day 1), 3 wks, 12 wks, and 6, 12, and 18 mos after initiation of treatment. Surveys included the FACT-B, Patient-Neurotoxicity Questionnaire (PNQ), Rotterdam Symptom Checklist (RSCL), Alopecia Patient Assessment, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). Results: 469/497 (94%) patients (363 on T-DM1, 106 on TH) completed surveys at any timepoint, ranging from 100% at baseline to 79% at 18 mos. Median age was 56 yrs (range 23-85). There were different patterns of deterioration and recovery seen over time in each group for QOL and other relevant symptoms. Compared with the T-DM1 group, the TH group had significantly lower mean total FACT-B scores, indicating poorer QOL from baseline to 12 weeks (p<0.001 for each timepoint); mean scores were similar between the groups at 6 and 12 mos, and significantly worse again in the TH group at 18 mos. The greatest mean change from baseline, and lowest FACT-B scores overall were reported in the TH group at 12 weeks. Moderate to severe sensory neuropathy was 8% at 12 weeks for patients receiving T-DM1 and reached its highest level of 15% by 18 mos. In comparison, moderate to severe sensory neuropathy was 35% at 12 weeks and 26% at 18 mos for patients on TH (p<0.001 at 12 weeks and p=0.018 at 18 mos). Hair loss at week 12 was 13% on T-DM1 compared to 77% on TH (p<0.001). Mean physical symptom distress was greater for TH at baseline, 3 and 12 weeks, and greater for T-DM1 at 1 year, with greatest symptom distress reported by the TH group at 12 weeks. Psychological distress was greatest for both groups at enrollment, though significantly greater with TH than T-DM1 at baseline, 12 weeks and 18 mos (groups were similar at 6 and 12 mos). There was limited impact on activity level impairment in both groups. Rates of employment were lowest for the TH group at 12 weeks (49% TH vs. 61% T-DM1, p=0.074) with significant differences seen at 3 and 12 weeks for percent work time missed due to health treatment, percent impairment while working, percent overall work impairment, and percent activity impairment, all favoring T-DM1. Conclusion: PROs differ between patients with Stage I HER2 positive breast cancer treated with T-DM1 vs. TH. T-DM1 treated patients had better QOL, less neuropathy and hair loss, and better work productivity, particularly during the first 12 weeks of treatment, and importantly, differences persist with longer-term follow-up. Citation Format: Ann Partridge, Yue Zheng, Shoshana Rosenberg, Richard Gelber, Shari Gelber, William Barry, Chau Dang, Denise Yardley, Steven Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio Wolff, Katherine Reeder-Hayes, Hope Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna Gadi, Michael Constantine, Kit Cheng, Frederick Briccetti, Bryan Schneider, Merrill Garrett, P. Kelly Marcom, Kathy Albain, Patricia Defusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel Jankowitz, Michelle DeMeo, Harold Burstein, Eric P. Winer, Ian Krop, Sara Tolaney. Patient reported outcomes from the adjuvant trastuzumab emtansine (T-DM1) vs. paclitaxel + trastuzumab (TH) (ATEMPT) trial (TBCRC 033) [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 PD10-02.