RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using drugs such as fulvestrant, anastrozole, or exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells and by lowering the amount of estrogen the body makes. It is not yet known whether giving fulvestrant and anastrozole, fulvestrant alone, or exemestane alone works better in treating breast cancer.

PURPOSE: This randomized phase III trial is studying fulvestrant and anastrozole to see how well it works compared to fulvestrant alone or exemestane alone in treating women with locally advanced or metastatic breast cancer.

OBJECTIVES:

Primary

• Compare progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive, locally advanced or metastatic breast cancer that relapsed or progressed during prior treatment with nonsteroidal aromatase inhibitors treated with fulvestrant with vs without anastrozole vs exemestane alone.

Secondary

• Compare the objective complete response (CR) and partial response (PR) rate and duration of response in patients treated with these regimens.
• Compare the clinical benefit (i.e., 6-month CR, PR, and stable disease) rate and duration of clinical benefit in patients treated with these regimens.
• Compare time to treatment failure in patients treated with these regimens.
• Compare the overall survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.

OUTLINE: This is a randomized, partially double-blind and placebo-controlled, multicenter study. Patients are stratified according to the setting in which prior nonsteroidal aromatase-inhibitor therapy was given (adjuvant therapy vs first-line therapy) and participating center. Patients are randomized to 1 of 3 treatment arms.

• Arm I (fulvestrant and anastrozole): Patients receive fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly. Patients receive oral anastrozole once daily.
• Arm II (fulvestrant and placebo): Patients receive fulvestrant as in arm I and oral placebo once daily.
• Arm III (exemestane alone): Patients receive oral exemestane once daily. In all arms, treatment repeats every month in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 750 patients (250 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the breast
• Locally advanced or metastatic disease
• Metastatic disease must be measurable or evaluable
• Patients with bone only metastases are eligible provided there is an evaluable site of bone metastasis that can be followed by x-ray, MRI, or CT scan
• Relapsed or progressed during prior treatment with single-agent nonsteroidal aromatase inhibitor (NSAI)*, meeting either of the following criteria:
• NSAI given as adjuvant therapy that lasted ≥ 12 months
• Achieved an objective complete response, partial response, or stable disease that lasted ≥ 6 months after prior first-line therapy with NSAI for locally advanced or metastatic disease
• Chemotherapy as part of the first-line therapy given before initiation of NSAI allowed NOTE: *Patients are required to continue to take NSAI until beginning of study treatment.
• No rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa or diffuse hepatic involvement)
• Hormone receptor status:
• Estrogen receptor (ER) and/or progesterone receptor positive
• No ER-unknown disease

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Postmenopausal, as defined by 1 of the following criteria:
• Aged 60 and over
• Aged 45 to 59 AND ≥ 12 months since last menstrual period with no prior hysterectomy
• Any age with prior bilateral oophorectomy

Performance status

• WHO 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• No thrombocytopenia

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN (unless due to bone metastases)
• No liver disease

Renal

• Creatinine < 1.97 mg/dL

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior tamoxifen as neoadjuvant or adjuvant therapy allowed

Chemotherapy

• See Disease Characteristics
• Prior neoadjuvant or adjuvant chemotherapy allowed

Endocrine therapy

• See Disease Characteristics
• No systemic corticosteroids that lasted > 15 days within the last 4 weeks

Surgery

• See Menopausal status

Other

• More than 4 weeks since prior investigational drugs
• Concurrent bisphosphonates for bone metastases allowed provided bisphosphonate therapy has been established for ≥ 6 months
• Concurrent initiation of bisphosphonate allowed provided patient has soft tissue or visceral metastases as the measurable or evaluable target lesion
• No concurrent anticoagulant therapy
• No concurrent unlicensed noncancer investigational agents