STOP-HER2: Stopping Trastuzumab in HER2+ MBC

Inclusion Criteria:

• Age ≥18 years

• Participants must have histologically or cytologically confirmed unresectablelocally advanced or metastatic invasive breast carcinoma that is HER2-positive byAmerican Society of Clinical Oncology/College of American Pathologists 2018criteria, as assessed by standard institutional guidelines (central testing is notrequired). Both estrogen receptor (ER)-positive/HER2-positive andER-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 yearswithout evidence of progressive disease according to RECIST 1.1 criteria. Thefollowing exceptions apply:

• Patients with history of brain-only progressive disease previously treated withlocal therapy (surgery and/or radiation therapy) are eligible, provided they meetall 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 thecompletion of CNS-directed therapy and screening radiographic study

• Minimum of 2 years (24 months) between completion of CNS-directed therapy andstudy start

• Participants with history of oligo-progression (i.e., progressive disease of asingle lesion) outside CNS treated with local treatment and/or change of endocrinetherapy only are eligible, provided they meet the following criteria:

• No evidence of interval progression between completion of local treatment orendocrine therapy change and screening radiographic study

• Minimum 2 years (24 months) between completion of local therapy or treatmentswitch and study start

• CT scan within 30 days of study start without definite evidence of progressivedisease in the opinion of the treating investigator.

• Available, representative archival formalin-fixed paraffin-embedded (FFPE) tumortissue block from primary and/or metastatic site. If tissue block is unavailable, 20unstained 10uM slides will be accepted (less than 20 slides may be acceptable withdocumentation of Sponsor-Investigator approval and would not require an eligibilityexception). Tumor tissue must be received by coordinating site prior to studyenrollment.

• 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, laboratorytests, and other study procedures

• Ability to understand the study requirements and document informed consentindicating awareness of the investigational nature and the risks of this study

• Participants with another prior or concurrent malignancy whose natural history ortreatment does not have the potential to interfere with the safety or efficacyassessment 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 compliancewith study requirements.

• All English- speaking patients will participate in the PRO measures. Patients thatdo not read or understand English are eligible to participate but will be exemptfrom the patient completed questionnaires