Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib

Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. * Locally advanced/unresectable or metastatic breast cancer with presence of brain metastases (Stage IV). * Histologically confirmed HER2+ breast carcinoma by ASCO-CAP guidelines, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology on most recent biopsy (primary tissue). * Currently receiving: (1) first-line trastuzumab/pertuzumab with or without endocrine therapy OR (2) second-line T-DM1 in the metastatic setting OR (3) adjuvant trastuzumab-based therapy or T-DM1 with isolated intracranial recurrence. Patients with de novo metastatic disease and brain metastases or isolated metastatic disease to the brain can enroll at time of initiation of trastuzumab/pertuzumab. Induction taxane therapy is not required and need to administer can be determined by the treating physician. Patients on trastuzumab alone are allowed if pertuzumab not tolerated. * Systemic disease otherwise stable per RECIST 1.1 or no evidence of extracranial disease. * Adequate hepatic and renal fu…