RATIONALE: Letrozole may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. It is not yet known whether letrozole is more effective than a placebo in treating patients with hormone receptor-positive breast cancer.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating postmenopausal women who have received letrozole and/or tamoxifen for breast cancer.

OBJECTIVES:

Primary

• Determine whether or not prolonged adjuvant hormonal therapy comprising letrozole vs placebo will improve disease-free survival of postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive breast cancer who have completed adjuvant letrozole and/or tamoxifen citrate.
• Compare the disease-free survival of patients treated with these regimens.

Secondary

• Compare overall survival of patients treated with these regimens.
• Compare breast cancer-free survival of patients treated with these regimens.
• Compare distant recurrence in patients treated with these regimens.
• Compare the incidence of osteoporotic-related fractures (e.g., Colles', hip, and spine) in these patients.
• Compare the incidence of arterial thrombotic events in these patients.

OUTLINE: This is a double-blind, multicenter, placebo-controlled, randomized study. Patients are stratified according to pathologic nodal status (negative vs positive), adjuvant tamoxifen citrate therapy (yes vs no), and lowest bone mineral density T score for lumbosacral spine, total hip, or femoral neck (> -2.0 vs ≤ -2.0 standard deviation). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral letrozole once daily.
• Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 3,840 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive carcinoma of the breast as seen by core needle or open biopsy
• Stage I, II, or IIIA primary tumor
• Received adjuvant hormonal therapy in duration of 57-63 months from the first dose (regardless of the number of missed doses) after breast cancer diagnosis meeting 1 of the following criteria:
• Aromatase inhibitor (AI)
• Combination of AI and up to 3 years of tamoxifen citrate for a total of 5 years
• No tamoxifen citrate during years 4 and 5 of the 5-year adjuvant hormonal therapy
• Must have completed adjuvant hormonal therapy within the past 6 months
• Must have undergone a bilateral mammogram within the past year (unilateral if patient had a mastectomy)
• Must have undergone a bone mineral density test within the past year
• Must have undergone a lumpectomy with axillary nodal staging followed by breast radiotherapy or a total mastectomy with axillary nodal staging
• Sentinel node biopsy alone allowed provided sentinel nodes were negative on H&E staining
• No evidence of recurrent breast cancer by history and physical within the past 3 months
• No diagnosis of contralateral breast cancer including ductal carcinoma in situ
• Estrogen receptor (ER)-positive and/or progesterone receptor-positive tumor
• Patients with a tumor considered to be borderline ER-positive and treated with tamoxifen citrate and/or AI are allowed

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal as defined by any 1 of the following criteria:
• Age ≥ 56 years with no spontaneous menses for ≥ 12 months prior to study entry
• Age ≤ 55 years with no spontaneous menses for ≥ 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) AND a documented estradiol level in the postmenopausal range
• Prior documented bilateral oophorectomy
• ECOG performance status 0 or 1
• Cholesterol ≤ grade 1 with or without cholesterol-lowering therapy meeting 1 of the following criteria:
• Must be met within the past year if patient meets any of the following criteria:
• History of hypercholesterolemia controlled with cholesterol-lowering therapy and/or therapeutic lifestyle changes
• History of ≥ 1 of the following risk factors for cardiovascular events:
• Diabetes
• Hypertension
• Obesity
• Tobacco use
• Hypertriglyceridemia
• Documented coronary artery disease
• Family history of premature coronary heart disease
• Must be met within the past 2 years for all other patients
• Not pregnant or nursing
• Negative pregnancy test
• No history of nontraumatic osteoporotic fracture of the wrist, hip, or spine
• No other malignancies unless disease-free for ≥ 5 years and, in the opinion of the investigator, at low risk for recurrence
• No other prior malignancy within the past 5 years except for the following:
• Carcinoma in situ of the cervix
• Colon carcinoma in situ
• Melanoma in situ
• Basal cell or squamous cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No other investigational agent within the past 30 days
• No other concurrent anticancer therapy
• No concurrent participation in any other hormonal therapy or placebo-controlled supportive therapy clinical trial
• No other concurrent hormonal therapy including any of the following:
• Hormonal agent for management of osteoporosis (e.g., raloxifene)
• Selective estrogen receptor modulators (e.g., raloxifene)
• Sex hormonal therapy (e.g., estrogen- or progesterone-replacement therapy including low-dose estrogen in the form of vaginal cream) or oral contraceptives
• Luteinizing hormone-releasing hormone agonists/antagonists (e.g., goserelin)
• Estradiol acetate
• Conjugated estrogen ring or estradiol hemihydrate vaginal tab allowed
• Other aromatase inhibitors
• Concurrent bisphosphonates allowed provided dose is as recommended for bone protection, not anticancer therapy