Conditions: Breast Cancer
Keywords: stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1918
Healthy volunteers: no

Brief summary:
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating in women with breast cancer who have already received 5 years of aromatase inhibitor therapy.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating women with primary breast cancer who have received 5 years of aromatase inhibitor therapy.

Detailed description:
OBJECTIVES:

Primary

* To compare the disease-free survival of women with primary breast cancer treated with letrozole vs placebo after completing approximately 5 years (i.e., 4½ - 6 years) of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane).

Secondary

* To compare the effect of these drugs on overall (all cause specific) mortality of these patients.
* To compare the incidence of contralateral breast cancer in patients treated with these drugs.
* To evaluate the long-term clinical and laboratory safety of aromatase inhibitor therapy, particularly cardiovascular morbidity and mortality (e.g., significant coronary artery disease, including myocardial infarction and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths); incidence of all bone fractures (with particular emphasis on hip and wrist fractures as indicators of osteoporosis); changes in bone density; and common toxicities.
* To compare overall quality of life (QOL) and menopausal-specific QOL of patients treated with these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), interval between last dose of aromatase inhibitor therapy and study randomization (\< 6 months vs 6 months to 2 years), and duration of prior tamoxifen citrate use (0 vs \< 2 years vs 2 - 4½ years vs \> 4½ years). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.
* Arm II: Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Patients undergo bone mineral density measurement by DEXA scan at baseline (if not done within 12 months of study entry), at 24 and 48 months during study therapy, and at the completion of study therapy. Some patients also complete quality-of-life questionnaires at baseline and at 12, 24, 36, 48, and 60 months.

After completion of study therapy, patients are followed annually.

Arms:
arm 1: Patients receive oral letrozole once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy. arm 2: Patients receive oral placebo once daily for up to 5 years in the absence of unacceptable toxicity, disease recurrence, or development of a second malignancy.

Interventions: intervention 1: letrozole intervention 2: placebo
Intervention descriptions: intervention 1: Given orally intervention 2: Given orally

Protocol document: