Safety and Efficacy Study of the Trifunctional Antibody Ertumaxomab to Treat Patients With Advanced or Metastatic Breast Cancer

Inclusion Criteria:

* Female gender, and if of child-bearing potential must have negative pregnancy test result within 2 days before enrolment and must agree to practice effective birth control during the study.
* Aged 18 years and older.
* Histologically or cytologically confirmed invasive breast cancer with stage IIIb or IV disease with documented progression.
* Measurable disease according to RECIST.
* Histologically documented advanced primary breast cancer or biopsy of metastatic site demonstrating HER-2/neu expression (HER-2/neu 1+ or 2+, determined by immunohistochemistry \[IHC\]). HER-2/neu 2+ patients must have a negative Fluorescence In Situ Hybridization \[FISH\] test result.
* Hormone receptor status Estrogen Receptors (ERs) positive and/or Progesterone Receptors (PRs) positive.
* No prior treatment with mouse or rat antibodies.
* Life expectancy of at least six months (if the life expectancy of a patient is unspecified she will be allowed to enter the study).
* An Eastern Cooperative Oncology Group (ECOG) performance score of £ 1.
* Patients must have had disease progression after hormonal therapy including at least one aromatase inhibitor.
* Adequate hematological, liver and kidney function:

  * Thrombocytes ³ 100000 / mm³ (= 100 x 109 /l)
  * Hemoglobin ³ 10 g/dl
  * Neutrophil count ³ 1500/mm³ (= 1.5 x 109 /l)
  * WBC ³ 3 X 109 /l
  * Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) ≤ 2.5 x upper limit of normal (ULN)
  * Serum bilirubin ≤ 2 x ULN
  * Creatinine ≤ 1.5 x ULN or clearance ³ 60 ml/min
* No life-threatening visceral disease.
* No known brain or central nervous system metastases.
* No symptomatic pleural effusions.
* No symptomatic pericardial effusions.
* No subjects whose only site of metastatic involvement is bone metastases with the exception of those with a measurable soft tissue component of the bone lesion seen with imaging that does not require palliative radiation intervention and/or the patient has a lytic bone lesion ³ 1 cm measured with radiography that can be followed for evidence of re-calcification.
* No history of relevant cardiovascular disease:

  * LVEF within the institutional ranges of normal as measured by echocardiogram or MUGA scan
  * No prior uncontrolled or symptomatic congestive heart failure NYHA ³ 2
  * No myocardial infarction within the past two years
  * No uncontrolled or symptomatic cardiac arrhythmias
* No severe dyspnea.
* No pulmonary dysfunction or need for continuous supportive oxygen inhalation.
* No other concurrent uncontrolled co-morbid illness.
* No other concurrent malignancy, except treated basal cell or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix.
* Patients with documented autoimmune diseases (such as lupus) are excluded from participation in the study unless a waiver is granted by the responsible medical monitor.
* Patients with a human immunodeficiency virus, hepatitis B or hepatitis C positive status are excluded from participation in the study.
* No prior or concurrent chemotherapy regimen for advanced or metastatic disease.
* Prior neo-adjuvant or adjuvant chemotherapy is allowed provided it was stopped at least six months before study entry.
* No concurrent hormone therapy (hormone therapy must be stopped at the screening visit).
* At least 4 weeks since prior radiotherapy.
* No concurrent immune therapy.
* No concurrent corticosteroid therapy.
* No regularly used medication for a health condition or comorbidity that might result in undue risk to the patient.
* No prior investigational treatment for advanced or metastatic disease.
* Able and willing to comply fully with the protocol.