Key PointsQuestionIs dual anti–human epidermal growth factor receptor 2 (ERBB2, formerly HER2) therapy with trastuzumab and pertuzumab effective after prior pertuzumab-based therapy for ERBB2-positive metastatic breast cancer?FindingsIn this phase 2 clinical trial, treatment with gemcitabine, trastuzumab, and pertuzumab after prior pertuzumab-based therapy for ERBB2-positive metastatic breast cancer was associated with a 3-month progression free survival rate of 73.3%. Treatment was well tolerated with no occurrences of symptomatic left ventricular systolic dysfunction.MeaningIn this study, dual anti-ERBB2 therapy with trastuzumab and pertuzumab after prior pertuzumab exposure was active and well tolerated.