Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer

Inclusion Criteria: * Adult males or females (aged 18 or older) with histologically confirmed, metastatic human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer * Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as a line of therapy and patients previously treated with T-DM1 are eligible. * Have not been treated with gemcitabine in the metastatic setting * Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status 2≤ * Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) * Adequate bone marrow function as indicated by the following: absolute neutrophil count (ANC) \>1500/µL; Platelets ≥100,000/µL; Hemoglobin \>10 g/dL * Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN) * Adequate liver function, as indicated by bilirubin ≤1.5x ULN, aspartic transaminase (AST) or alanine transaminase (ALT) \<2x ULN unless related to metastatic breast cancer to the liver (in which case AST/ALT \< 5x ULN is allowed). * Signed informed consent * Adequate birth control in sexually active women of childbearing potential Exclusion Criteria: * Active uncontrolled infection or major concurrent illness which in the opinion of the investigator would render the participant unsafe to proceed with the study * Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS disease (documented by brain magnetic resonance imaging \[MRI\]) off corticosteroids for at least 1 month potential participants are eligible. * Women who are pregnant or lactating * Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin) * Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation) * Other concomitant active malignancies * History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias * Ejection fraction \<50% or below the lower limit of the institutional normal range, whichever is lower * Hypersensitivity to any of the study medications * Untreated psychiatric conditions preventing informed consent