RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is more effective in postmenopausal women who have received hormone therapy for early-stage breast cancer. PURPOSE: This randomized phase III trial is comparing two different regimens of letrozole in preventing cancer in postmenopausal women who have received 4-6 years of hormone therapy for hormone receptor-positive, lymph node-positive, early-stage breast cancer.
OBJECTIVES: Primary * Compare the disease-free survival (DFS) of postmenopausal women treated with continuous letrozole for 5 years vs intermittent letrozole over a 5-year period. Secondary * Compare overall survival of patients treated with these two regimens. * Compare distant DFS of these patients. * Compare breast cancer-free interval of these patients. * Compare sites of first DFS failure in these patients. * Compare second (nonbreast) malignancies in these patients. * Compare deaths without prior cancer events in these patients. * Compare adverse events resulting from these two regimens. OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and type of prior endocrine therapy (selective estrogen receptor modulators \[SERMs\] alone vs aromatase inhibitors \[AIs\] alone vs both SERMs and AIs each for at least 1 month). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral letrozole daily for 5 years. * Arm II: Patients receive oral letrozole daily for the first 9 months of years 1 through 4, followed by 12 months in year 5. After completion of study therapy, patients are followed annually.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
4,884
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Faulkner Hospital
Boston, Massachusetts, United States
Armidale Hospital
Armidale, New South Wales, Australia
Bankstown - Lidcombe Hospital
Bankstown, New South Wales, Australia
Southern Highlands Cancer Center
Bowral, New South Wales, Australia
Disease-free Survival (DFS)
Duration of time from randomization to the first indication of the following events: invasive recurrence at local (including recurrence restricted to the breast after breast conserving treatment), regional or distant sites; a new invasive cancer in the contralateral breast; any second (non-breast) invasive malignancy; or a death without prior cancer event. Appearance of DCIS or LCIS either in the ipsilateral or in the contralateral breast was not be considered as an event for DFS. In the absence of an event, DFS was censored at the date of last follow-up visit.
Time frame: 5-year estimates, reported at a median follow-up of 60 months
Overall Survival
Duration of time from randomization to death from any cause, or was censored at the date last known alive. (Note, for patients who withdrew consent or were lost to follow-up but follow-up for survival was possible through hospital or registry records, OS was censored at the date last known alive rather than date of last follow-up/withdrawn consent).
Time frame: 5-year estimates, reported at a median follow-up of 60 months
Distant Recurrence-free Interval (DRFI)
Duration of time from randomization to the first indication of invasive breast recurrence at a distant site. In the absence of an event, DRFI was censored at the date of last follow-up visit or date or death without distant recurrence.\* \*This endpoint replaced DDFS, which was specified in the protocol
Time frame: 5-year estimates, reported at a median follow-up of 60 months
Breast Cancer-free Interval
Duration of time from randomization to the first indication of the following events: invasive breast recurrence at local, regional or distant sites; a new invasive cancer in the contralateral breast (second non-breast malignancies are ignored). In the absence of an event, BCFI was censored at the date of last follow-up visit or date of death without prior breast cancer event.
Time frame: 5-year estimates, reported at a median follow-up of 60 months
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Concord Repatriation General Hospital
Concord, New South Wales, Australia
Breast Center
Gateshead, New South Wales, Australia
Port Mcquarie Base Hospital
Port Macquarie, New South Wales, Australia
Prince of Wales Private Hospital
Randwick, New South Wales, Australia
Tamworth Base Hospital
Tamworth, New South Wales, Australia
...and 154 more locations