Bone Density and Bone Loss in Postmenopausal Women With Breast Cancer Receiving Treatment in Clinical Trial IBCSG-1-98

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as bone mineral density testing and x-ray, help measure bone loss in women receiving treatment for breast cancer. The test results may help doctors plan better treatment. PURPOSE: This phase III trial is studying bone density and bone loss in postmenopausal women with breast cancer receiving treatment in clinical trial IBCSG-1-98.

Detailed Description
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OBJECTIVES: Compare the effects on bone mineral density (BMD) in the L2-L4 (posterio-anterior) region of the spine and hip by assessing bone density in postmenopausal women with breast cancer receiving treatment on protocol IBCSG-1-98. Compare the incidence of radiological gross changes and fractures identified from spine x-rays (T4-L4) in these patients (in groups 1 and 2). Use longitudinal BMD measurements to estimate a linear rate of bone loss based on mixed effect models. Identify serum markers for bone loss to determine how they correlate with osteoporosis, microfractures, clinical fractures, and breast cancer-related bone events. OUTLINE: This is a multicenter study and a substudy of protocol IBCSG-1-98. Patients are assigned to 1 of 3 groups according to the length of treatment they have undergone on protocol IBCSG-1-98. Group 1 (prior to or at the end of the second year of treatment on protocol IBCSG-1-98): Patients undergo bone mineral density (BMD) testing of the L2-L4 spine and hip at baseline and years 1, 2, 3, and 4 from baseline. They also undergo x-rays of the T4-L4 spine at baseline and years 1, 3, and 4 from baseline. Group 2 (after 2 years but before the end of the third year of treatment on protocol IBCSG-1-98): Patients undergo BMD testing of the L2-L4 spine and hip at baseline and years 1, 2, and 3 from baseline. They also undergo x-rays of the T4-L4 spine at baseline and years 2 and 3 from baseline. Group 3 (after 3 years but before the end of the fifth year of treatment on protocol IBCSG-1-98): Patients undergo BMD testing of the L2-L4 spine and hip at baseline and years 1 and 2 from baseline (for patients in 4th year of treatment) or year 1 from baseline (for patients in 5th year of treatment). Patients undergo blood collection at baseline and periodically during study for biomarker correlative study. PROJECTED ACCRUAL: A total of 660 patients will be accrued for this study.

Official Title
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Investigating Bone Density and Bone Loss Without Baseline Information

Conditions
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Breast Cancer, Osteoporosis

Intervention / Treatment
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* Other: laboratory biomarker analysis
* Procedure: Dual energy X-ray absorptiometry (DEXA)
* Procedure: Spine X-ray


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of breast cancer Resected disease Enrolled on protocol IBCSG-1-98 Receiving adjuvant endocrine therapy comprising 1 of the following regimens: Letrozole Tamoxifen Letrozole after 2 years of tamoxifen Tamoxifen after 2 years of letrozole Not yet completed 5 years of treatment No breast cancer recurrence or second primary cancer No known, symptomatic bone disease, including osteomalacia or osteogenesis imperfecta No prior registration to protocol IBCSG-1-98 Bone Mineral Density substudy Hormone receptor status: Estrogen receptor-positive and/or progesterone receptor-positive tumor PATIENT CHARACTERISTICS: Female Postmenopausal No uncontrolled thyroid or parathyroid disease, Cushing's disease, or other pituitary diseases No malabsorption syndrome or clinically relevant vitamin D deficiency No patients for whom the bone density determination is impossible PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 1 year since prior and no concurrent anticonvulsants More than 6 weeks since prior and no concurrent corticosteroids (at doses > the equivalent of 5 mg/day prednisone) for > 2 weeks total No prior or concurrent sodium fluoride (at daily doses ≥ 5 mg/day) for > 1 month More than 12 months since prior and no concurrent anabolic steroids More than 6 months since prior treatment, either investigational or not, for the prevention of osteoporosis (excluding calcium or cholecalciferol [vitamin D]) No concurrent raloxifene Concurrent therapeutic intervention for osteoporosis comprising bisphosphonates allowed Concurrent warfarin allowed provided it is given for ≤ 4 weeks

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifen for 5 years<br>Patients treated with tamoxifen for 5 years after randomisation. | Other: laboratory biomarker analysis<br>* Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.<br>Procedure: Dual energy X-ray absorptiometry (DEXA)<br>* Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.<br>Procedure: Spine X-ray<br>* Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.<br>|
| Experimental: Letrozole for 5 years<br>Patients treated with letrozole for 5 years after randomisation. | Other: laboratory biomarker analysis<br>* Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.<br>Procedure: Dual energy X-ray absorptiometry (DEXA)<br>* Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.<br>Procedure: Spine X-ray<br>* Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.<br>|
| Experimental: Tamoxifen 2 years plus letrozole 3 years<br>Patients treated with tamoxifen for 2 years and afterwards with letrozole for 3 years. | Other: laboratory biomarker analysis<br>* Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.<br>Procedure: Dual energy X-ray absorptiometry (DEXA)<br>* Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.<br>Procedure: Spine X-ray<br>* Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.<br>|
| Experimental: Letrozole 2 years plus tamoxifen 3 years<br>Patients treated with letrozole for 2 years and afterwards with tamoxifen for 3 years. | Other: laboratory biomarker analysis<br>* Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.<br>Procedure: Dual energy X-ray absorptiometry (DEXA)<br>* Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.<br>Procedure: Spine X-ray<br>* Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative percent change of bone mineral density (BMD) form baseline to after 2, 3, 4, or 5 years of treatment on protocol IBCSG-1-98 |  | 5 years after randomisation to BIG 1-98 | 
| Recovery of BMD at 1 year after the completion of treatment on protocol IBCSG-1-98 |  | 6 years after randomisation to BIG 1-98 | 
| Proportion of patients with BMD below the absolute threshold value for osteoporosis |  | 5 years after randomisation to BIG 1-98 | 
| Relative percent change in markers of bone resorption from baseline to after 2, 3, 4, or 5 years of treatment on protocol IBCSG-1-98 |  | 5 years after randomisation to BIG 1-98 | 
| Recovery of the markers of bone resorption at 1 year after the completion of treatment on protocol IBCSG-1-98 |  | 6 years after randomisation to BIG 1-98 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer