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

ETOP IBCSG Partners Foundation

Status and phase: Completed; Phase 3

Conditions: Osteoporosis; Breast Cancer

Treatments: Other: laboratory biomarker analysis; Procedure: Dual energy X-ray absorptiometry (DEXA); Procedure: Spine X-ray

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00369850

CDR0000482381

EU-20623 (Other Identifier)

NOVARTIS-2026703019

IBCSG-1-98-BS (Other Identifier)

IBCSG-18-98-BS (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 458 patients

Sex: Female

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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458 participants in 4 patient groups

Tamoxifen for 5 years

Experimental group

Description:

Patients treated with tamoxifen for 5 years after randomisation.

Treatment:

Procedure: Dual energy X-ray absorptiometry (DEXA)

Procedure: Spine X-ray

Other: laboratory biomarker analysis

Letrozole for 5 years

Experimental group

Description:

Patients treated with letrozole for 5 years after randomisation.

Treatment:

Procedure: Dual energy X-ray absorptiometry (DEXA)

Procedure: Spine X-ray

Other: laboratory biomarker analysis

Tamoxifen 2 years plus letrozole 3 years

Experimental group

Description:

Patients treated with tamoxifen for 2 years and afterwards with letrozole for 3 years.

Treatment:

Procedure: Dual energy X-ray absorptiometry (DEXA)

Procedure: Spine X-ray

Other: laboratory biomarker analysis

Letrozole 2 years plus tamoxifen 3 years

Experimental group

Description:

Patients treated with letrozole for 2 years and afterwards with tamoxifen for 3 years.

Treatment:

Procedure: Dual energy X-ray absorptiometry (DEXA)

Procedure: Spine X-ray

Other: laboratory biomarker analysis