• Response rate [ Designated as safety issue: No ]
  
• Progression-free survival [ Designated as safety issue: No ]
  
• Correlation of HER2/neu status with response [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the response rate in women with refractory locally advanced or metastatic primary adenocarcinoma of the breast treated with 17-N-allylamino-17-demethoxygeldanamycin.
• Determine the progression-free survival of patients treated with this drug.
• Correlate HER2/neu status with response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin IV over 1-6 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at day 30, every 10-12 weeks until disease progression, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 14 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary adenocarcinoma of the breast

  • Locally advanced or metastatic disease

• At least 1 unidimensionally measurable lesion ≥ 2 cm by conventional techniques OR ≥ 1 cm by MRI or spiral CT scan

  • Outside prior irradiation field
• Disease progression after prior hormonal therapy in estrogen receptor (ER)-positive and/or indolent disease
• Disease progression after prior treatment with OR contraindication to an anthracycline and a taxane-based regimen (as adjuvant therapy or for metastatic disease)
• Not amenable to curative surgery or radiotherapy

• No known brain or leptomeningeal metastases requiring active therapy

  • Asymptomatic previously treated metastases allowed

• Hormone receptor status:

  • ER status known

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Sex

• Female

Menopausal status

• Premenopausal or postmenopausal

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 1.5 times ULN (3 times ULN if liver metastases are present)

Renal

• Creatinine ≤ ULN OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• QTc ≤ 450 msec for men (470 msec for women)
• LVEF ≥ 40% by MUGA
• Deep venous thrombosis or other clinically significant thromboembolic event within the past 6 months allowed provided patient is clinically stable on anticoagulation therapy
• No New York Heart Association class III or IV heart failure
• No myocardial infarction within the past year
• No active ischemic heart disease within the past year
• No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs
• No congenital long QT syndrome
• No left bundle branch block
• No poorly controlled angina
• No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No severe or unstable angina within the past 6 months
• No symptomatic congestive heart failure within the past 6 months
• No cerebrovascular accident or transient ischemic attack within the past 6 months

Pulmonary

• Pulmonary embolus within the past 6 months allowed provided patient is clinically stable on anticoagulation therapy

• No symptomatic pulmonary disease including any of the following:

  • Dyspnea
  • Chronic obstructive pulmonary disease
  • Restrictive lung disease
• No oxygen requirement

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2 weeks after study participation
• No serious allergy to eggs (e.g., hypotension, dyspnea, anaphylaxis, or edema)
• No known HIV positivity
• No other active infection
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent trastuzumab (Herceptin^®)

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered (excluding alopecia and neurotoxicity)

Endocrine therapy

• See Disease Characteristics
• At least 2 weeks since prior hormonal therapy

Radiotherapy

• See Disease Characteristics
• More than 2 weeks since prior radiotherapy
• No prior radiotherapy that potentially included the heart in the field (e.g., mantle)
• No prior radiotherapy to the chest

Surgery

• More than 4 weeks since prior surgery
• More than 6 months since prior coronary or peripheral artery bypass grafting

Other

• Concurrent zoledronate for bone metastases or hypercalcemia allowed
• No concurrent medications that prolong or may prolong QTc interval
• No other concurrent antineoplastic agents