Inclusion Criteria:  Centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines.  Have unresectable locally advanced or metastatic disease.  If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab or pertuzumab received for advanced HER2+ disease. Have received 4-8 cycles (21 day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-]) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1  CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants may have any of the following:  No evidence of brain metastases Untreated brain metastases which are asymptomatic and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane  Previously treated brain metastases which are asymptomatic  Brain metastases previously treated with local therapy must not have progressed since treatment  Exclusion Criteria:  Prior treatment with any anti-HER2 and/or anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug) Unable to undergo contrast MRI of the brain  CNS Exclusion - Based on screening brain MRI and clinical assessment  Symptomatic brain metastasis Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent) Any untreated brain lesion in an anatomic site which may pose risk to participant Known or suspected leptomeningeal disease (LMD) Poorly controlled (>1/week) seizures, or other persistent neurologic symptoms