Inclusion Criteria:

• Pathologically confirmed locally advanced or metastatic breast cancer.
• HER2-expressing primary or metastatic tumor
• Must have received at least two prior regimens with HER2. Trastuzumab must have been a component of one of these regimens. Adjuvant therapies do not count unless progression on adjuvant treatment. No limit to prior therapies
• Measurable disease with RECIST criteria.
• Clinical progression during or since the patient's most recent systemic therapy
• LVEF WNL of institution
• ECOG 0 or 1
• Last dose of chemotherapy, radiotherapy, surgery, ablative therapy, tyrosine kinase inhibitor, or any investigational therapy ≥2 weeks
• Administration of the last dose of biological therapy ≥4 weeks
• Last dose of trastuzumab must be ≥1 week prior to start, if given on a weekly schedule, or ≥3 weeks prior to start, if previously administered on an every 3 week schedule.
• Resolution of toxic effects of surgery, radiotherapy, chemotherapy, ablative therapy, or investigational therapy to baseline or Grade 1, except alopecia (NCI CTCAE Version 3.0).

• Organ and marrow function as defined below:

  • Hemoglobin ≥8.0 g/dL
  • ANC ≥1200/µL
  • Platelets ≥75,000 /µL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase
  • (AST) ≤ 2.5 x upper limit of normal, or ≤3.0 x ULN if secondary to liver metastases.
  • Alkaline phosphatase ≤2.5 x ULN, or ≤3.0 x ULN if secondary to liver metastases. If the alkaline phosphatase elevation is secondary to bone metastases, then any level of alkaline phosphatase is acceptable if GGT <1.5 x ULN.
  • Serum bilirubin ≤1.5 x ULN
  • Serum albumin ≥3.0 g/dL
  • Prothrombin time and partial thromboplastin time ≤1.5 x ULN
  • Serum creatinine ≤1.5 x ULN
• Negative pregnancy test

Exclusion Criteria:

• Prior treatment with Hsp90 inhibitor.
• Prior Grade 4 or intolerable AE secondary to trastuzumab. Includes Grade 3/4 infusion reactions or Grade 3/4 symptomatic heart failure
• Medication or food that is a CYP3A inhibitor or inducer.
• Within last 6 months: cardiac disease - acute coronary syndrome or unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident or significant co-morbid condition or disease which, in the judgment of the investigator, would place the patient at undue risk
• Grade 3 or 4 hemorrhagic event within 6 months.
• Known HIV positivity.
• Baseline QT corrected, QTcF >470 ms. Patients with LBBB are eligible regardless of QTcF, as long as serum troponin is normal or undetectable.
• Sinus bradycardia <50 bpm. Sinus bradycardia secondary to pharmacologic therapy may enroll if stopping therapy normalizes heart rate.
• Prior malignancies within 3 years other than non-melanomatous skin cancers, non-muscle-invasive bladder cancer and carcinoma in situ of the cervix.
• Active keratitis or keratoconjunctivitis

• Active brain metastasis (e.g., requiring therapy with steroids or radiation therapy; or with intracranial progression 4 weeks after the completion of radiation therapy) uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. If clinically stable brain metastasis (previously treated or untreated)are present pt is eligible.

  • Pregnancy