Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the breast
Metastatic (stage IV) disease at primary diagnosis or at relapse after curative intent therapy

Local or central laboratory confirmedHER2/neu* overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by the following:

3+ overexpression (in > 30% of invasive tumor cells) by immunohistochemistry (IHC)
2+ or 3+ overexpression (in ≤ 30% of invasive tumor cells) by IHC AND demonstrates HER2/neu gene amplification by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)
HER2/neu gene amplification by FISH/CISH (> 6 HER2/neu gene copies per nucleus, or a FISH/CISH ratio [HER2 gene copies to chromosome 17 signals] of ≥ 2.2) NOTE: *Patients with a negative or equivocal overall result (FISH/CISH ratio of < 2.2, ≤ 6.0 HER2/neu gene copies per nucleus, or staining scores of 0, 1+, 2+, or 3+ [in ≤ 30% of neoplastic cells] by IHC) are not eligible
Formalin-fixed paraffin-embedded tumor specimen available
No CNS metastases (including leptomeningeal involvement)
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG performance status 0-2
Life expectancy > 6 months
Absolute granulocyte count > 1,500/mm³
Platelet count > 75,000/mm³
Hemoglobin > 10 g/dL
Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
Total bilirubin ≤ 1.5 times ULN (< 3 times ULN for patients with Gilbert's disease)
AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN for patients planning to receive paclitaxel-based therapy)
LVEF ≥ 50% by MUGA or ECHO
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Must be accessible for study treatment and follow-up
No history of other malignancies, except adequately treated ductal carcinoma in situ or lobular carcinoma in situ, adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor (non-breast) with no evidence of disease for ≥ 5 years

No serious cardiac illness or condition including, but not limited to, any of the following:

History of documented congestive heart failure
Systolic dysfunction (LVEF < 50%)
High-risk uncontrolled arrhythmias (i.e., ventricular tachycardia, high-grade atrioventricular block, or supraventricular arrhythmias that are not adequately rate-controlled)
Unstable angina pectoris requiring anti-anginal medication
Clinically significant valvular heart disease
Evidence of transmural infarction on ECG
Inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
New York Heart Association class III-IV functional status

No serious illness or medical condition that would not allow the patient to be managed according to the protocol including, but not limited to, any of the following:

History of significant neurologic or psychiatric disorder that would impair the ability to obtain informed consent or limit compliance with study requirements
Active uncontrolled infection
Serious or nonhealing wound, ulcer, or bone fracture
No peripheral neuropathy ≥ grade 2

No gastrointestinal (GI) tract disease resulting in an inability to take oral medication including, but not limited to, any of the following:

Malabsorption syndrome
Requirement for IV alimentation
Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

No history of allergic or hypersensitivity reactions to any study drug or their excipients or to compounds with similar chemical composition to any of the study drugs

Prior allergic reactions to taxanes are allowed provided they were adequately treated and, according to the treating physician, would not prohibit further treatment with taxanes

PRIOR CONCURRENT THERAPY:

Recovered from all prior therapy
No prior chemotherapy, immunotherapy, biological therapy, or anti-HER2/neu-targeted therapy for recurrent or metastatic breast cancer
At least 12 months since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting
At least 12 months since prior anti-HER2/neu-targeted therapy in the neoadjuvant or adjuvant setting
Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, or metastatic setting allowed

At least 2 weeks since prior radiotherapy in the adjuvant or metastatic setting

Prior radiotherapy to a solitary metastatic lesion allowed provided there is documented disease progression after completion of radiotherapy
More than 30 days (or 5 half-lives) since prior investigational drugs
At least 7 days since prior and no concurrent CYP3A4 inhibitors (6 months for amiodarone)
At least 14 days since prior and no concurrent CYP3A4 inducers
No prior surgical procedures affecting absorption (e.g., resection of stomach or small bowel)
No concurrent palliative radiotherapy
No other concurrent anticancer treatment
No other concurrent investigational drugs for breast cancer