Trastuzumab and Pertuzumab in Treating Patients With Unresectable Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Previous Trastuzumab

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer of 1 of the following stages:
• Metastatic disease (stage IV)
• Inoperable locally advanced disease
• Disease progression after prior neoadjuvant chemotherapy required
• Disease progression on or after trastuzumab (Herceptin®) based-therapy
• Received 1-3 prior trastuzumab-based regimens
• HER2/neu-positive tumor, defined as 3+ by fluorescent in situ hybridization
• Measurable disease, defined as at least 1 lesion that can be measured in at least one dimension
• No clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT scan or MRI
• Brain and/or leptomeningeal metastases allowed if patient has stable lesions after standard treatment (surgery or radiotherapy), is asymptomatic on neurological exam, and is not receiving corticosteroid therapy to control symptoms
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Male or female
• Menopausal status not specified
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 75,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Alkaline phosphatase < 5 times ULN
• AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
• LVEF above lower limit of normal by echocardiogram or MRI
• No clinical signs or symptoms of heart failure
• No uncontrolled hypertension (i.e., blood pressure ≥ 180/100 mm Hg)
• No significant valvular disease (i.e., aortic or mitral regurgitation of 3 or 4+/4+ severity or stenosis of either valve)
• No history of uncontrolled cardiac arrhythmia
• No symptomatic or asymptomatic myocardial infarction
• No angina pectoris requiring medication
• No other documented significant cardiac event
• No poorly controlled diabetes mellitus (i.e., fasting blood sugar ≥ 200 mg/dL)
• No history of hypersensitivity reaction to trastuzumab
• No AIDS
• No nonmalignant condition requiring ≥ 20 mg of prednisone (or equivalent)
• No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
• No ongoing liver disease, including viral or other hepatitis, alcohol abuse, or cirrhosis
• No other serious medical illness
• No medical or psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• More than 3 weeks since prior investigational anticancer agents
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), major surgery, or immunotherapy
• More than 4 weeks since prior radiotherapy except short-course palliative radiotherapy for bone pain
• More than 2 weeks since prior and no concurrent oral hormonal therapy
• More than 4 weeks since prior fulvestrant
• No prior doxorubicin hydrochloride or doxorubicin HCl liposome at a cumulative dose of > 360 mg/m^2
• No prior mitoxantrone hydrochloride at a cumulative dose of > 120 mg/m^2
• No prior epirubicin hydrochloride at a cumulative dose of > 600 mg/m^2
• No prior idarubicin at a cumulative dose of > 90 mg/m^2
• No concurrent radiation therapy, including for symptomatic bone metastases