A Phase 3 interventional study of Letrozole and Letrozole in Breast Cancer, sponsored by ETOP IBCSG Partners Foundation. Completed at 164 sites in 20 countries. Open to female participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by ETOP IBCSG Partners Foundation · Phase 3, Interventional, and Prevention
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
Secondary
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.
After completion of study therapy, patients are followed annually.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 4,884 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →ETOP IBCSG Partners Foundation is the lead sponsor of 50 studies on the registry; 5 are open to participants now.
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DISEASE CHARACTERISTICS:
Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the following criteria:
Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a sequential combination of both
PATIENT CHARACTERISTICS:
Must be postmenopausal by any of the following criteria:
Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range)
PRIOR CONCURRENT THERAPY:
Any type of prior adjuvant therapy allowed including, but not limited to, any of the following:
Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily)
Drug: Letrozole
Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -\> 36 mo) plus 1 x 12 mo in yr 5 -\> 48 months
Drug: Letrozole
Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously
Film-coated tablet, oral use, 2.5 mg daily, 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -\> 36 mo) plus 1 x 12 mo in yr 5 -\> 48 months
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
| Milestone | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| Started | 2441 | 2443 |
| Completed | 2426 | 2425 |
| Not completed | 15 | 18 |
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.
| percentage of patients | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| Disease-free Survival (DFS) | 87.5 (86 to 88.8) | 85.8 (84.2 to 87.2) |
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).
| percentage of patients | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| Overall Survival | 93.7 (92.6 to 94.7) | 94.3 (93.2 to 95.2) |
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
| percentage of patients | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| Distant Recurrence-free Interval (DRFI) | 92.5 (91.3 to 93.5) | 93.2 (92 to 94.2) |
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.
| percentage of patients | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| Breast Cancer-free Interval | 91.2 (89.9 to 92.3) | 90.9 (89.6 to 92.1) |
Collected over during or within 30 days after stopping study treatment. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A: Continuous Letrozole | 170/2,426 (7%) | 1,004/2,411 (41.6%) | 2,257/2,411 (93.6%) |
| Arm B: Intermittent Letrozole | 146/2,425 (6%) | 1,052/2,417 (43.5%) | 2,261/2,417 (93.5%) |
| Event | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| HypertensionVascular disorders | 517/2411 | 584/2417 |
| Pain - JointMusculoskeletal and connective tissue disorders | 151/2411 | 139/2417 |
| Hot flashes/flushesVascular disorders | 70/2411 | 59/2417 |
| FractureInjury, poisoning and procedural complications | 66/2411 | 62/2417 |
| Mood alteration - depressionPsychiatric disorders | 54/2411 | 61/2417 |
| InsomniaPsychiatric disorders | 59/2411 | 52/2417 |
| Fatigue (asthenia, lethargy, malaise)General disorders | 58/2411 | 48/2417 |
| Pain - BoneMusculoskeletal and connective tissue disorders | 58/2411 | 46/2417 |
| Pain - MuscleMusculoskeletal and connective tissue disorders | 54/2411 | 53/2417 |
| ObesityMetabolism and nutrition disorders | 37/2411 | 42/2417 |
| Event | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole |
|---|---|---|
| Pain - JointMusculoskeletal and connective tissue disorders | 1506/2411 | 1453/2417 |
| Hot flashes/flushesVascular disorders | 1240/2411 | 1217/2417 |
| OsteoporosisMusculoskeletal and connective tissue disorders | 1113/2411 | 1119/2417 |
| Fatigue (asthenia, lethargy, malaise)General disorders | 1025/2411 | 954/2417 |
| InsomniaPsychiatric disorders | 983/2411 | 961/2417 |
| Pain - MuscleMusculoskeletal and connective tissue disorders | 841/2411 | 818/2417 |
| Mood alteration - depressionPsychiatric disorders | 767/2411 | 762/2417 |
| Pain - BoneMusculoskeletal and connective tissue disorders | 634/2411 | 613/2417 |
| HypertensionVascular disorders | 539/2411 | 493/2417 |
| FractureInjury, poisoning and procedural complications | 148/2411 | 136/2417 |
Randomized patients, regardless of eligibility status; exceptions were patients who immediately withdrew consent prior to treatment initiation and declined all participation, patients determined to be without adequate documentation of informed consent, and/or patients at a participating center determined not to be compliant with protocol procedures
| Age, Customized(Participants) | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole | Total |
|---|---|---|---|
| <55 | 668 | 671 | 1339 |
| 55-59 | 504 | 496 | 1000 |
| 60-64 | 451 | 471 | 922 |
| 65-69 | 400 | 375 | 775 |
| 70+ | 383 | 412 | 795 |
| Sex: Female, Male(Participants) | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole | Total |
|---|---|---|---|
| Female | 2426 | 2425 | 4851 |
| Male | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole | Total |
|---|---|---|---|
| White/Caucasian | 2199 | 2211 | 4410 |
| Black | 10 | 9 | 19 |
| Asian | 119 | 121 | 240 |
| Other | 97 | 83 | 180 |
| Unknown | 1 | 1 | 2 |
| Region of Enrollment(participants) | Arm A: Continuous Letrozole | Arm B: Intermittent Letrozole | Total |
|---|---|---|---|
| Hungary | 78 | 77 | 155 |
| United States | 21 | 19 | 40 |
| Japan | 93 | 99 | 192 |
| United Kingdom | 217 | 216 | 433 |
| Switzerland | 159 | 159 | 318 |
| India | 8 | 8 | 16 |
| Russia | 22 | 21 | 43 |
| Spain | 137 | 134 | 271 |
| New Zealand | 10 | 9 | 19 |
| Austria | 88 | 92 | 180 |
| Sweden | 104 | 105 | 209 |
| Belgium | 509 | 520 | 1029 |
| Denmark | 223 | 218 | 441 |
| Italy | 287 | 291 | 578 |
| South Africa | 28 | 28 | 56 |
| Australia | 182 | 171 | 353 |
| Chile | 70 | 70 | 140 |
| France | 14 | 16 | 30 |
| Peru | 33 | 33 | 66 |
| Germany | 146 | 145 | 291 |
Showing the first 100 of 164 sites across 20 countries.
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ETOP IBCSG Partners Foundation