A Phase 1b/2, Multicenter, Open-label, Dose-Finding Study to Evaluate the Safety and Antitumor Activity of Patritumab Deruxtecan in Participants with HER2 Positive Unresectable Locally Advanced Breast Cancer or Metastatic Breast Cancer.

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: - Has histologically confirmed HER2+ locally advanced unresectable breast cancer or metastatic breast cancer - Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART) - Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load before allocation - Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable - Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 7 days before start of study intervention Arm 1: - Has received at least a minimum of 2 and a maximum of 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting - Had disease progression on or after any previous trastuzumab deruxtecan (T-DXd) treatment Arm 2: -Has received no more than 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting Arm 3: -Has received and had disease progression from T-DXd treatment in any setting and a maximum of 3 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting. T-DXd must be the most recent therapy received before enrollment. Exclusion Criteria: The main exclusion criteria include but are not limited to the following: - Uncontrolled or significant cardiovascular disease - History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/interstitial lung disease - Has clinically severe respiratory compromise - Has any history of or evidence of any current leptomeningeal disease - Has clinically significant corneal disease - Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection - HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease - Known additional malignancy that is progressing or has required active treatment within the past 3 years - Evidence of spinal cord compression or brain metastases - Has an active infection requiring systemic therapy - Concurrent active HBV and HCV infection - Has had major surgical procedure (excluding placement of vascular access) less than 28 days Arm 3 ONLY - Has received prior treatment with tucatinib, lapatinib, or neratinib, or any investigational HER2-targeted tyrosine kinase inhibitors in the locally advanced or metastatic setting