A Clinical Trial to Determine the Efficacy of Five Years of Letrozole Compared to Placebo in Patients Completing Five Years of Hormonal Therapy Consisting of an Aromatase Inhibitor (AI) or Tamoxifen Followed by an AI in Prolonging Disease-Free Survival in Postmenopausal Women With Hormone Receptor Positive Breast Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed invasive carcinoma of the breast by core needle or final
pathological evaluation of the surgical specimen

- Clinical stage I, II, or IIIA primary tumor for patients who received
neoadjuvant chemotherapy

- Primary tumor t1-3 on pathologic evaluation and ipsilateral nodes pN0, pN1
(pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b for patients who received
adjuvant chemotherapy

- Received adjuvant hormonal therapy after breast cancer diagnosis for a duration of
57-63 months from the first dose (regardless of the number of missed doses) with 1 of
the following:

- Aromatase inhibitor* (AI)

- Combination of up to 3 years of tamoxifen citrate followed by an AI for a total
of 5 years

- No tamoxifen citrate during years 4 and 5 of 5-year adjuvant hormonal
therapy NOTE: *Adjuvant AI therapy must be discontinued at the time of
randomization

- 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)

- Mammogram not required if patient has a prophylactic contralateral 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

- Nodal staging with sentinel node biopsy alone is 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 bilateral breast cancer, including ductal carcinoma in situ
(synchronous or metachronous)

- Estrogen receptor (ER)-positive and/or progesterone receptor-positive tumor

- Patients with a tumor considered to be borderline hormone receptor-positive that
was treated with tamoxifen citrate and/or AI are allowed

PATIENT CHARACTERISTICS:

- Female

- Postmenopausal as defined by any 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:

- Criteria must be met within the past year if patient has any of the following:

- 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

- Criteria must be met within the past 2 years for all other patients

- Not pregnant or nursing

- 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