Gemcitabine Hydrochloride, Trastuzumab, and Pertuzumab in Treating Patients with Stage IV Metastatic HER2-Positive Breast Cancer after Prior Trastuzumab/Pertuzumab or Pertuzumab-Based Therapy

Inclusion Criteria

• Stage IV HER2 (+) breast cancer
• Histologically documented HER2 (+) breast cancer as defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplification of >= 2.0 of primary or metastatic site; results from the local lab are acceptable
• Eastern Cooperative Oncology Group (ECOG) performance status 0 -1
• Prior treatment with trastuzumab + pertuzumab (HP)-based or pertuzumab-based therapy in the neoadjuvant/adjuvant, unresectable, locally advanced, or metastatic setting
• =< 3 prior chemotherapies in the metastatic setting; prior anthracycline, taxane, gemcitabine, and anti-HER2 agents (i.e. trastuzumab, pertuzumab, lapatinib, neratinib, TDM-1, etc.) are allowed; if patients received prior gemcitabine, it could not have been combined with pertuzumab; patients should have progression of disease on current therapy
• Measurable or non-measurable disease
• Left ventricular ejection fraction (LVEF) >= 50%
• White blood cell (WBC) count of >= 3000/ul
• Absolute neutrophil count (ANC) >= 1000/ul
• Platelets >= 100,000/ul
• Hemoglobin >= 10.0 g/dl
• Bilirubin =< 1.5 mg/dl
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Alkaline phosphatase =< 5 x ULN
• Creatinine =< 1.5 mg/dl
• Patients with “treated and stable” brain lesions of a duration of >= 2 months may be enrolled

Exclusion Criteria

• History of prior unstable angina, myocardial infarction, congestive heart failure (CHF), uncontrolled ventricular arrhythmias within 12 months
• History of prior >= G 3 hypersensitivity (HSR) or any toxicity to trastuzumab or pertuzumab that warranted permanent cessation of this agent
• History of hepatitis B or C
• Pregnant patients