Background: Trastuzumab-anns was launched in the US in July 2019 as the first trastuzumab biosimilar for treating human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer (BC) and metastatic gastric cancer. Information on how trastuzumab-anns is being used in clinical practice is beginning to evolve. Objectives: We aimed to investigate initial use of trastuzumab-anns for BC management during the first 12 months after product launch. Methods: We performed a retrospective, observational analysis of BC patients (≥18 y) who initiated trastuzumab-anns from July 2019 to June 2020 using structured patient-level data from the nationwide de-identified Flatiron Health EHR-derived database. The database is longitudinal, demographically and geographically diverse, and includes more than 2.2 million US cancer patients (primarily treated in a community setting) from >280 cancer clinics. Results: First use of trastuzumab-anns was in early stage BC (eBC) and occurred 4 days after product launch. 2,149 patients with eBC and 799 patients with metastatic BC (mBC) met eligibility and were included in the analysis. Most patients were White (58%) and ≥ 55 y of age (70%), with ECOG scores of 0/1 (86%) and hormone receptor status being positive (67%). Patients were primarily covered by commercial insurance and/or Medicare, Medicaid or other government programs (M/M/G) (commercial only: 30%; M/M/G only: 15%; commercial combined with M/M/G: 12%; commercial and/or M/M/G plus patient assistance program: 28%). 50% of eBC patients were trastuzumab-naïve prior to initiation of trastuzumab-anns therapy, while most of mBC patients (76%) were previously exposed to trastuzumab. Among naïve patients, median time from BC diagnosis to initiation of trastuzumab-anns were 34 days for eBC and 30 days for mBC. For previously exposed patients who transitioned to trastuzumab-anns, information regarding line of therapy was not available, thus, we were not able to capture whether patients were switched to trastuzumab-anns within the current line or initiated as a new line, but majority (79%) were switched within 28 days of last infusion of reference product. Conclusions: Early evidence in the first 12 months of product launch suggests physicians are comfortable initiating or transitioning patients to trastuzumab-anns. Future analyses will allow better understanding the long-term experience of trastuzumab-anns patients, including efficacy and tolerability.