RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of perifosine in treating patients who have recurrent, refractory, locally advanced, or metastatic breast cancer.

OBJECTIVES:

• Determine the objective tumor response rate in patients with recurrent or refractory, locally advanced or metastatic breast cancer treated with perifosine.
• Determine the toxicity of this drug in these patients.
• Determine the stable disease rate, time to disease progression, objective response duration, and duration of stable disease in patients treated with this drug.
• Correlate potential endpoints, including phosphorylated ERK, PKB, and SAPK, phosphorylated PKC alpha, beta, and gamma isoforms, p21 ^WAF1; and activated capase-3 in tumor biopsies, with clinical outcome in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive a loading dose of oral perifosine on days 1 and 2 and once daily on days 3-21 during course 1. Patients receive oral perifosine once daily on days 1-21 in each subsequent course. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) may receive 2 additional courses beyond the CR.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 6-12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

  • Recurrent or refractory, locally advanced or metastatic disease

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR 10 mm by spiral CT scan
  • Previously irradiated lesions are not considered measurable unless they have demonstrated progression before study entry
  • No measurable disease limited to bone lesions

• No known brain metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No history of hemolytic disorder

Hepatic

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN (5 times ULN if liver metastases present)

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No evidence of cardiac dysfunction

Gastrointestinal

• No history of biliary flow obstruction
• No abnormalities of the gastrointestinal tract that would preclude study drug absorption
• No active peptic ulcer disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No poorly controlled diabetes mellitus
• No other uncontrolled illness
• No prior allergic reactions to compounds of similar chemical or biological composition to perifosine
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 2 prior lines of chemotherapy for advanced disease, excluding adjuvant chemotherapy
• Prior adjuvant chemotherapy allowed
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• At least 4 weeks since prior endocrine therapy

  • Multiple lines of endocrine therapy for advanced disease allowed

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

  • Prior radiotherapy for metastatic disease allowed

Surgery

• No prior major gastric surgery
• Prior surgery, including for metastatic disease, allowed

Other

• No other concurrent anticancer or investigational agents
• No concurrent antiretroviral therapy in HIV-positive patients
• Concurrent bisphosphonates allowed