The primary purpose(s) of this study is to determine the highest tolerated dose of tanespimycin and to determine anti-tumor activity (via objective response rate) of tanespimycin in patients with breast cancer who have not previously responded to Herceptin

Inclusion Criteria:

• Age >=18 years

• KPS performance status >= 70%

• For the Phase 1 portion of the trial, all patients must have a histologically confirmed solid tumor malignancy. For the Phase 2 portion of the trial, patients must have metastatic breast cancer with HER2 amplification by FISH or 3+ HER2 overexpression by immunohistochemistry ("IHC") Patients may have had either progressive disease within 3 months following last dose of adjuvant treatment with trastuzumab OR progressive disease following initial therapy for metastatic disease with trastuzumab (trastuzumab may have been administered with cytotoxic chemotherapy, hormonal therapy or as single agent.) Patients who have received trastuzumab single agent therapy (without documented progressive disease) followed by trastuzumab combination therapy remain eligible for this study at the time of disease progression. Patients must have measurable disease by RECIST

• All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade <= 2 (except for alopecia)

• The following laboratory results, within 10 days of KOS-953 administration:

• Hemoglobin >= 8.5 g/dL

• Absolute neutrophils count >= 1.5 x 10*9* /L

• Platelet count >= 75 x 10*9* /L

  • Serum bilirubin <= 2 x ULN
  • AST and ALT <= 2 x ULN
  • Serum creatinine <= 2 x ULN
  • Signed informed consent

Exclusion Criteria:

• Documented hypersensitivity reaction of CTCAE Grade >= 3 to prior therapy containing Cremophor (for those patients who receive the Tanespimycin Injection only) or Herceptin
• Pregnant or breast-feeding women
• Known active CNS metastases
• Except for trastuzumab (Herceptin®) administered between 7-21 days prior to first tanespimycin (KOS-953) administration, administration of any other chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 14 days prior to receipt of study medication. Patients should be 6 weeks from last dose of nitrosourea
• Severe dyspnea at rest caused by complications of advanced malignancy or requiring supplementary oxygen therapy
• Congestive heart failure, or a left ventricular ejection fraction (LVEF) less than 50% assessed by multigated radionuclide angiography scan or echocardiography
• Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient
• Patients with previous malignancies unless free of recurrence for at least 5 years except cured basal cell carcinoma of the skin, carcinoma-in-situ of either the uterine cervix or urinary bladder, or Stage T1 or T2 prostate cancer whose PSA is < 2 ng/mL