A Randomized, Blinded, Phase 2 Study of Letrozole Plus the Farnesyl Transferase Inhibitor ZARNESTRA (R115777) and Letrozole Plus Placebo in the Treatment of Advanced Breast Cancer After Antiestrogen Therapy

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed breast cancer in 1 of the following disease
states:

- Locally advanced

- Locoregionally recurrent

- Metastatic

- Documented disease progression on or after antiestrogen therapy, given in 1 of the
following ways:

- As adjuvant therapy (for at least 12 months)

- As first-line therapy for advanced disease, on which the patient had an
objective response (partial or complete) or stable disease for at least 6 months

- Measurable disease

- If the sole indicator lesion is in a previously irradiated area, recurrence of
the lesion must be biopsy proven

- No rapidly progressive, life-threatening metastases, including:

- CNS metastases

- Diffuse lymphangitis carcinomatosa of the lung

- Metastases occupying more than 1/3 of the liver

- Hormone receptor status:

- Estrogen receptor- or progesterone receptor-positive (i.e., primary or secondary
tumor tissue positive by any assay)

PATIENT CHARACTERISTICS:

Age

- See Menopausal status

Sex

- Female

Menopausal status

- Postmenopausal, defined as any of the following:

- Over 50 years of age and no menstruation for more than 12 months

- Any age with castrate levels of follicle-stimulating hormone

- Underwent prior bilateral oopherectomy

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count normal

- Platelet count normal

Hepatic

- Bilirubin no greater than 2 mg/dL

- AST and ALT no greater than 2.5 times upper limit of normal (ULN)

Renal

- Creatinine no greater than 1.5 times ULN

Other

- No other malignancy within the past 5 years except contralateral breast carcinoma,
basal cell or nonmetastatic squamous cell skin cancer, carcinoma in situ of the
cervix, or stage I carcinoma of the cervix

- No symptomatic peripheral neuropathy

- No known or suspected allergy to letrozole or imidazole drugs (e.g., clotrimazole,
ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole,
tioconazole, or terconazole)

- No coexisting medical condition that would interfere with study procedures and/or
results

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No more than 1 prior chemotherapy regimen, given as adjuvant therapy or for
metastatic disease (not both)

Endocrine therapy

- See Disease Characteristics

- No prior systemic endocrine therapy (including aromatase inhibitors) except
antiestrogen therapy (e.g., tamoxifen)

Radiotherapy

- See Disease Characteristics

Surgery

- Not specified

Other

- At least 30 days since prior participation in another investigational study

- No prior farnesyl transferase inhibitor therapy

- No other concurrent anticancer treatment

- Concurrent bisphosphonates allowed for bone metastases present at baseline