A Randomized, Controlled, Open-Label Trial of Empiric Prophylactic vs. Delayed Use of Zoledronic Acid for Prevention of Bone Loss in Postmenopausal Women With Breast Cancer Initiating Therapy With Letrozole After Tamoxifen
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of breast cancer
- Stage I, II, or IIIA disease
- Completed ≤ 6 years of adjuvant tamoxifen therapy
- Total baseline lumbar spine or femoral neck bone mineral density T-score below -2.0
standard deviation (e.g., a patient with a T-score of -2.1 in ineligible; a patient
with a T-score of -1.9 is eligible)
- No clinical or radiological evidence of recurrent or metastatic disease
- Hormone receptor status:
- Estrogen receptor- and/or progesterone receptor-positive
PATIENT CHARACTERISTICS:
Age
- Postmenopausal
Sex
- Female
Menopausal status
- Postmenopausal, defined by 1 of the following:
- Over 55 years of age with cessation of menses
- 55 years of age and under with spontaneous cessation of menses for > 1 year
- 55 years of age and under with spontaneous cessation of menses for ≤ 1 year, but
amenorrheic (e.g., spontaneous or secondary to hysterectomy) with postmenopausal
estradiol levels (< 5 ng/dL)
- Undergone bilateral oophorectomy
Performance status
- ECOG 0-2
Life expectancy
- At least 5 years
Hematopoietic
- WBC ≥ 3,000/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
Renal
- Creatinine < 2.0 mg/dL
- No hypercalcemia (i.e., calcium > 1 mg/dL above ULN within the past 6 months)
- No hypocalcemia (i.e., calcium > 0.5 mg/dL below lower limit of normal within the
past 6 months)
Other
- No uncontrolled infection
- No uncontrolled diabetes mellitus
- No uncontrolled thyroid dysfunction
- No disease affecting bone metabolism (e.g., hyperparathyroidism, hypercortisolism,
Paget's disease, or osteogenesis imperfecta)
- No malabsorption syndrome
- No uncontrolled seizure disorder associated with falls
- No known hypersensitivity to zoledronate or other bisphosphonates, letrozole,
calcium, or cholecalciferol (vitamin D)
- No mental illness that would preclude giving informed consent
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No other non-malignant systemic disease
- No clinical or radiologic evidence of existing fracture in the lumbar spine and/or
total hip
- No history of fracture with low intensity or not associated with trauma
- No contraindication to spinal dual energy x-ray absorptiometry (DEXA) due to any of
the following:
- History of surgery at the lumbosacral spine, with or without implantable devices
- Scoliosis with a Cobb angle > 15° at the lumbar spine
- Immobility, hyperostosis, or sclerotic changes at the lumbar spine
- Evidence of sufficient sclerotic abdominal aorta that would interfere with DEXA
scan
- Any disease of the spine that would preclude proper acquisition of a lumbar
spine DEXA
- Considered reliable
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No concurrent chemotherapy
Endocrine therapy
- See Disease Characteristics
- Prior parathyroid hormone allowed provided it was not administered for > 1 week
- More than 6 months since prior anabolic steroids or growth hormone
- More than 12 months since prior endocrine therapy (including estrogen) except for the
following:
- Tamoxifen
- Insulin
- Oral hypoglycemics
- Thyroid hormone
- Steroid inhalers
- More than 12 months since prior systemic corticosteroids except short-term
corticosteroids to prevent or treat chemotherapy-induced nausea and vomiting or acute
respiratory illness
- Concurrent short-term corticosteroids allowed
- No other concurrent hormonal therapy
- No concurrent parathyroid hormone
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- Prior systemic sodium fluoride allowed provided it was not administered for > 3
months within the past 2 years
- More than 3 weeks since prior oral bisphosphonates
- More than 2 weeks since prior and no concurrent drugs known to affect the skeleton
(e.g., calcitonin, mithramycin, or gallium nitrate)
- More than 30 days since prior systemic investigational drugs and/or devices
- More than 7 days since prior topical investigational drugs
- No prior IV bisphosphonates
- No prior aromatase inhibitor therapy
- No concurrent calcitonin, sodium fluoride, or Tibolone
- No other concurrent anticancer therapy
- No other concurrent bisphosphonates
- No other concurrent investigational drugs or devices