Breast Cancer, Osteoporosis
Conditions
Keywords
osteoporosis, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer
Brief summary
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
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.
Interventions
OTHERlaboratory biomarker analysis
Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.
Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.
PROCEDURESpine X-ray
Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.
Sponsors
ETOP IBCSG Partners Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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 |
Countries
Australia, France, Italy, New Zealand, Peru, South Africa, Spain, Switzerland
Outcome results
None listed