GW572016 and Trastuzumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER2/Neu

Inclusion Criteria:

* Histologically or cytologically confirmed breast cancer
* Metastatic disease
* Measurable or evaluable disease
* HER2/neu overexpression (2+ or 3+) confirmed by immunohistochemistry and/or HER2 gene amplification by fluorescence in situ hybridization
* Brain metastases treated by surgery and/or radiotherapy allowed provided the following criteria are met:

  * Neurologic status stable 2 weeks after discontinuing dexamethasone
  * No concurrent anticonvulsants that induce metabolism (e.g., phenytoin, carbamazepine, or phenobarbital)
* 18 and over
* Male or female
* Karnofsky 70-100%
* Life expectancy, At least 12 weeks
* Hematopoietic

  * Absolute granulocyte count ≥ 1,500/mm\^3
  * Platelet count ≥ 100,000/mm\^3
  * Hemoglobin ≥ 9 g/dL
  * AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if patient has liver metastases)
  * Bilirubin \< 1.5 mg/dL
  * Creatinine clearance \> 30 mL/min
* Cardiovascular

  * LVEF \> 50%
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 4 weeks after study participation
* Adequate venous access
* Able to swallow and retain oral medication
* Prior adjuvant/neoadjuvant chemotherapy allowed
* More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin.
* More than 4 weeks since prior radiotherapy
* More than 4 weeks since prior major surgery
* Recovered from all prior therapy
* More than 28 days since prior participation in another investigational study
* More than 28 days since prior investigational drugs

Exclusion Criteria:

* extensive tumor, pleural effusions, or parenchymal masses) resulting in dyspnea at rest
* uncontrolled brain metastases or leptomeningeal disease
* prior myocardial infarction
* pre-existing cardiac dysfunction (e.g., congestive heart failure)
* clinically significant cardiac disease
* angina pectoris
* symptomatic intrinsic pulmonary disease (e.g., asthma or chronic obstructive pulmonary disease) resulting in dyspnea at rest
* pregnant or nursing
* active infection
* known hypersensitivity to Chinese Hamster Ovary cell proteins or any component of this product
* known immediate or delayed hypersensitivity reaction or idiosyncrasy to products of similar chemical composition as study drug
* known contraindications to trastuzumab (Herceptin\^®)
* malabsorption syndrome
* disease significantly affecting gastrointestinal function
* psychiatric disorder that would preclude study compliance
* other serious illness or condition
* concurrent biologic therapy
* prior cumulative dose of doxorubicin \> 400 mg/m\^2 (including liposomal doxorubicin)
* concurrent hormonal therapy\*
* concurrent glucocorticoids
* concurrent radiotherapy
* prior major resection of the stomach or small bowel that could affect absorption of GW572016
* concurrent cytotoxic therapy
* other concurrent anticancer therapy
* other concurrent investigational drugs during and for 28 days after study treatment
* concurrent administration of any of the following medications or substances:
* Antibiotics

  * Clarithromycin
  * Erythromycin
  * Troleandomycin
  * Ciprofloxacin
  * Rifampin
  * Norfloxacin
  * Rifabutin
* HIV antivirals

  * Delaviridine
  * Indinavir
  * Nelfinavir
  * Ritonavir
  * Saquinavir
  * Efavirenz
  * Nevirapine
  * Amprenavir
  * Lopinavir
* Anticonvulsants

  * Phenytoin
  * Carbamazepine
  * Phenobarbital
* Antidepressants

  * Fluoxetine
  * Nefazodone
  * Fluvoxamine
* Antifungals

  * Itraconazole
  * Ketoconazole
  * Fluconazole
  * Voriconazole
* Antacids (within 1 hour before and after study drug administration)
* Cimetidine
* Amiodarone
* Diltiazem
* Pioglitazone
* Hypericum perforatum (St. John's wort)
* Grapefruit or grapefruit juice
* Rifabutin
* Diethyldithiocarbamate
* Gestodene
* Mifepristone
* Modafinil