RATIONALE: Drugs used in chemotherapy, such as irinotecan and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with etoposide works in treating patients with recurrent, locally advanced, or metastatic breast cancer.

OBJECTIVES:

Primary

• To determine the response rate, as assessed by RECIST criteria, in patients with recurrent locally advanced or metastatic breast cancer treated with irinotecan hydrochloride and etoposide after prior exposure to anthracycline, taxane, and capecitabine therapy.

Secondary

• To determine the median time to progression in these patients.
• To determine the response duration and survival in these patients.
• To measure the type and rate of grade 3 or greater toxicity of this treatment regimen in these patients.

OUTLINE: Patients receive irinotecan hydrochloride IV on days 1 and 15 and oral etoposide on days 1-14. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study therapy, patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

DISEASE CHARACTERISTICS:

• Diagnosis of locally advanced or metastatic breast cancer

  • Recurrent, refractory or progressive disease after receiving prior anthracycline, taxane, and capecitabine therapy

    • Prior anthracycline and taxane therapy may have been as neoadjuvant, or adjuvant therapy if disease progression is documented within a year of completing that agent
    • Received prior capecitabine therapy for metastatic or recurrent disease

• Measurable disease

  • Bone metastases requires other disease present that can be measured

• No brain metastases, unless documented to be controlled post-completion of local therapy (surgery and/or radiation therapy) for at least 4 weeks

• No meningeal carcinomatosis

• No malignant effusion as the only site of disease recurrence

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• Performance status of 0-2
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 40 mL/min
• Hemoglobin ≥ 10 g/dL
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal or hyperbilirubinemia < grade 1 (unless due to Gilbert syndrome with elevated total but normal levels of conjugated bilirubin)
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other non-breast malignancy, except nonmelanoma skin cancer
• No other serious underlying medical condition, that in the opinion of the treating physician, would make study protocol unreasonably hazardous for the patient or would preclude the patient's ability to comply with the study protocol

PRIOR CONCURRENT THERAPY:

• See Disease Characteristic
• Recovered from all prior chemotherapy or radiotherapy to NCI CTC grade ≤ 1
• Unlimited documented prior chemotherapy regimens allowed
• No prior irinotecan hydrochloride or etoposide
• No Hypericum perforatum (St. John's wort) 14 days prior to, during, or 7 days after completion of study therapy
• At least 7 days since prior and no concurrent phenytoin, carbamazepine, phenobarbital, or any other enzyme-inducing anticonvulsant drug (EIACD)
• No concurrent aprepitant

Adverse events were assessed at the end of each 28-day cycle of treatment