Exemestane Compared With Tamoxifen in Treating Postmenopausal Women With Breast Cancer

OBJECTIVES:

• Compare the efficacy and tolerability of adjuvant exemestane versus adjuvant tamoxifen in postmenopausal women with early breast cancer.
• Compare the relapse-free survival and overall survival of patients treated with these drugs.
• Compare the incidence of contralateral breast cancer in patients treated with these drugs.
• Compare the safety and long-term tolerability of these drugs in these patients.
• Compare the quality of life of patients treated with these drugs.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to estrogen receptor (ER)/progesterone receptor (PgR) status (ER positive vs ER negative/PgR positive vs ER positive/PgR unknown), prior chemotherapy (none vs taxane-based vs anthracycline-based vs other), and nodal status (negative vs 1-3 nodes positive vs 4 or more nodes positive). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral tamoxifen once daily
• Arm II: Patients receive oral exemestane once daily. Treatment in both arms continues for a minimum of 5 years in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at months 3 and 12 during study.

Patients are followed at least annually.

PROJECTED ACCRUAL: Approximately 4,400 patients (2,200 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed early adenocarcinoma of the breast

• Completely excised by surgery with curative intent (R0)

• Any N OR
• Any primary tumor greater than 3 cm OR
• Any primary tumor grade III and greater than 1 cm
• M0
• No positive supraclavicular nodes
• Hormone receptor status:

• Estrogen and/or progesterone receptor positive

PATIENT CHARACTERISTICS:

Age:

• Any age
• See Menopausal status

Sex:

• Female

Menopausal status:

• Postmenopausal

• Any age with bilateral oophorectomy or amenorrhea for at least 5 years OR
• Age 50 or over:

• Natural amenorrhea for at least 1 year OR
• Chemotherapy-induced amenorrhea for at least 2 years OR
• Radiation-induced amenorrhea (at least 3 months since prior radiotherapy) OR
• Under age 50:

• If amenorrheic for less than 5 years (any cause) or prior hysterectomy without bilateral surgical oophorectomy, follicle-stimulating hormone must be assayed to confirm postmenopausal status

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count greater than 100,000/mm3
• WBC greater than 3,000/mm3

Hepatic:

• SGOT or SGPT less than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No uncontrolled cardiac disease
• No unstable angina
• No congestive heart failure or arrhythmia requiring medical therapy
• No myocardial infarction within the past 3 months

Other:

• No severe osteoporosis
• No other malignancies within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
• No other serious concurrent disease that would preclude study
• No psychiatric disorders that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior neoadjuvant chemotherapy
• No more than 10 weeks since completion of prior adjuvant chemotherapy

Endocrine therapy:

• No prior adjuvant hormonal therapy for breast cancer
• No prior neoadjuvant hormonal therapy (prior to surgery) for duration of more than 4 weeks
• At least 4 weeks since prior hormone replacement therapy

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics
• No more than 10 weeks since completion of curative surgery

Other:

• No other concurrent investigational agents or participation in another clinical study (except adjuvant cytotoxic chemotherapy studies)
• Concurrent bisphosphonates allowed