Characteristics
|
ABCSG-12a
|
ZO-FASTb
|
Z-FASTc
|
AZUREd
|
NSABP B-34e
|
| Population |
1803 Premenopausal women with stage I/II, endocrine-receptor-positive breast cancer, receiving goserelin (3.6 mg, every 28 days) to induce artificial menopause |
1065 Postmenopausal women with stage I–IIIa, endocrine-receptor-positive breast cancer receiving letrozole (2.5 mg daily) for 5 years |
602 Postmenopausal women with stage I–IIIa, endocrine-receptor-positive breast cancer receiving letrozole (2.5 mg daily) for 5 years |
3360 Pre- and postmenopausal women with stage II/III breast cancer receiving standard chemotherapy and/or endocrine therapy |
3323 Pre- and postmenopausal women with stage I–III breast cancer receiving standard chemotherapy and/or endocrine therapy |
| Treatment |
Patients were randomly assigned to receive anastrozole (1 mg daily) or tamoxifen (20 mg daily) with or without zoledronate (4 mg every 6 months) for 3 years |
Patients were randomly assigned to receive immediate zoledronate (4 mg every 6 months for 5 years) or delayed zoledronate (initiated only for fracture or high risk thereof) |
Patients were randomly assigned to receive immediate zoledronate (4 mg every 6 months for 5 years) or delayed zoledronate (initiated only for fracture or high risk thereof) |
Patients were randomly assigned to receive zoledronate 4 mg every 4 weeks for 6 doses, then every 3 months for 8 doses, then every 6 months for 5 doses until 5 years |
Patients were randomly assigned to receive oral clodronate (1600, mg daily) for 3 years |
| Outcomes |
Endocrine therapy+zoledronate resulted in a 36% reduction in the risk of disease progression (HR=0.64; 95% CI 0.46–0.91; P=0.01) at 36 months' follow-up and continued to reduce the risk at 62 months' follow-up (HR=0.68; 95% CI, 0.51–0.91; P=0.009). In addition, there was an overall survival benefit at 76 months' follow-up (HR=0.59; P=0.04). Benefits were restricted to patients older than 40 years on study entry (n=1390) |
The immediate-zoledronate group had a 41% reduction in the risk of disease progression (HR=0.59; 95% CI 0.36–0.96; P=0.0314) at 36 months' follow-up and continued to reduce the risk at 60 months' follow-up (HR=0.66; P=0.0375) |
Disease progression rates at 61 months' follow-up were similar between the immediate- and delayed-zoledronate groups (9.8 (95% CI 6–10.3) versus 10.5 (95% CI 6.6–14.4), P=0.628) |
No significant difference between the two groups at 59 months' follow-up. In women who were postmenopausal for at least 5 years before study entry, the zoledronate group had a 25% reduction in the risk of disease progression (HR=0.75; 95% CI, 0.59–0.96; P=0.02) and a 26% reduction in the risk of death (HR=0.74; 95% CI, 0.55–0.98; P=0.04) |
No significant difference between the two groups at 90.7 months' follow-up. In women who were 50 years or older on study entry, the clodronate group had a 25% reduction in the risk of disease progression (HR=0.75; 95% CI, 0.57–0.99; P=0.045), but not for overall survival (HR=0.80; 95% CI, 0.61–1.04; P=0.094) |
