Zoledronic Acid in the Prevention of Cancer Treatment Related Bone Loss in Postmenopausal Women Receiving Letrozole for Breast Cancer.

Phase 3

Completed

Brief Summary: Post-menopausal breast cancer patients will receive letrozole 2.5 mg daily for the treatment of breast cancer and will be randomized to a treatment group to receive either upfront zoledronic acid 4 mg IV 15-minute infusion every 6 months or delayed start zoledronic acid 4 mg IV 15-minute infusion every 6 months. Delayed start zoledronic acid will be initiated when either the Bone Mineral Density T-score is below -2 Standard Deviations at either the lumbar spine or hip or any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the month 36 scheduled visit. Letrozole 2.5 mg will be given daily for 5 years.

Recruitment & Eligibility

Inclusion Criteria

Stage I-IIIa breast cancer
Postmenopausal or recently postmenopausal
Recent surgery for breast cancer
Estrogen Receptor positive and/or progesterone receptor positive hormone receptor status
No prior treatment with letrozole

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria

Metastatic disease
Invasive bilateral disease
Clinical or radiological evidence of existing fracture in spine or hip
Prior treatment with IV bisphosphonates in the past 12 months
Current treatment with oral bisphosphonates ( must be discontinued within 3 weeks of baseline evaluation)
Use of Tibolone within 6 months
Prior use of parathyroid hormone for more than 1 week
Previous or concomitant malignancy
Abnormal renal function
History of disease effecting bone metabolism

Other protocol-defined exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
Upfront Zoledronic Acid	Letrozole	Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
Delayed Zoledronic Acid	Zoledronic acid	Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
Upfront Zoledronic Acid	Zoledronic acid	Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
Delayed Zoledronic Acid	Letrozole	Zolendronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.

Primary Outcome Measures

Name	Time	Method
Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy.	Baseline, 12 months	Bone Mineral Density (g/cm\^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA).

Secondary Outcome Measures

Name	Time	Method
Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy.	Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.	Bone Mineral Density (g/cm\^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA)
Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy.	Baseline, 5 years.	Bone Mineral Density (g/cm\^2) of the Lumbar Spine (L1-L4)as measured by dual energy x-ray absorptiometry (DXA)
Percentage Change in Bone Mineral Density (BMD) of the Total Hip at 12 Months, 2 Years, 3 Years, 4 Years and 5 Years After Therapy.	Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.	Bone Mineral Density (g/cm\^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA)
Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline	Baseline,3 years	At 3 years of therapy the percentage of participants with fractures as detected by X-ray and/ or bone scan.