STOP-HER2: Stopping Trastuzumab in HER2+ MBC

Inclusion Criteria: * Age ≥18 years * Participants must have histologically or cytologically confirmed unresectable locally advanced or metastatic invasive breast carcinoma that is HER2-positive by American Society of Clinical Oncology/College of American Pathologists 2018 criteria, as assessed by standard institutional guidelines (central testing is not required). Both estrogen receptor (ER)-positive/HER2-positive and ER-negative/HER2-positive will be eligible. * Participants with ER-positive disease should continue endocrine therapy. * Participants must be currently receiving first-line anti-HER2 therapy (any regimen) for metastatic disease and must have been on this therapy for at least 3 years without evidence of progressive disease according to RECIST 1.1 criteria. The following exceptions apply: * Patients with history of brain-only progressive disease previously treated with local therapy (surgery and/or radiation therapy) are eligible, provided they meet all the following study criteria: * Asymptomatic * Not requiring anti-convulsant for symptomatic control * Not requiring corticosteroids * No evidence of interim central nervous system (CNS) progression between the completion of CNS-directed therapy and screening radiographic study * Minimum of 2 years (24 months) between completion of CNS-directed therapy and study start * Participants with history of oligo-progression (i.e., progressive disease of a single lesion) outside CNS treated with local treatment and/or change of endocrine therapy only are eligible, provided they meet the following criteria: * No evidence of interval progression between completion of local treatment or endocrine therapy change and screening radiographic study * Minimum 2 years (24 months) between completion of local therapy or treatment switch and study start * CT scan within 30 days of study start without definite evidence of progressive disease in the opinion of the treating investigator. * Available, representative archival formalin-fixed paraffin-embedded (FFPE) tumor tissue block from primary and/or metastatic site. If tissue block is unavailable, 20 unstained 10uM slides will be accepted (less than 20 slides may be acceptable with documentation of Sponsor-Investigator approval and would not require an eligibility exception). Tumor tissue must be received by coordinating site prior to study enrollment. * ECOG performance status 0-1 * For intervention arm only (cohort 2): willingness to stop anti-HER2 systemic therapy * Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures * Ability to understand the study requirements and document informed consent indicating awareness of the investigational nature and the risks of this study * Participants with another prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of this trial are eligible Exclusion Criteria: * Participants who are receiving any investigational agents to treat breast cancer * Participants with psychiatric illness/social situations that would limit compliance with study requirements. * All English- speaking patients will participate in the PRO measures. Patients that do not read or understand English are eligible to participate but will be exempt from the patient completed questionnaires