Zoledronate in Treating Osteopenia or Osteoporosis in Postmenopausal Women Receiving Letrozole for Stage I, Stage II, or Stage IIIA Primary Breast Cancer

OBJECTIVES:

Primary

• Assess changes in total lumbar spine bone mineral density (BMD) from baseline to 12 months in postmenopausal women treated with zoledronate for osteopenia or osteoporosis and letrozole for hormone receptor-positive, stage I-IIIA primary breast cancer.

Secondary

• Determine changes in total lumbar spine BMD from baseline to 2, 3, 4, and 5 years in these patients.
• Determine changes in femoral neck BMD from baseline to 1, 2, 3, 4, and 5 years in these patients.
• Determine time to disease progression in these patients.

OUTLINE: This is an open-label, multicenter study.

• Adjuvant aromatase inhibitor therapy: Patients receive oral letrozole daily for up to 5 years in the absence of disease progression or unacceptable toxicity.
• Osteoporosis management: Patients receive zoledronate IV over 15 minutes on day 1. Patients also receive oral elemental calcium twice daily and oral vitamin D daily for 6 months. Treatment repeats every 6 months for up to 5 years in the absence of disease progression or unacceptable toxicity.

Patients undergo total lumbar spine and hip (femoral neck) bone density testing by dual energy x-ray absorptiometry (DXA) at baseline and annually for 5 years.

After completion of study therapy, patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of localized breast cancer

• Stage I-IIIA disease
• Adequately treated breast cancer

• No clinical or radiological evidence of recurrent or metastatic disease
• Baseline total lumbar spine or femoral neck bone mineral density T-score < -2.0 standard deviation (e.g., a patient with a T score of -2.1 is eligible)
• Hormone-receptor status:

• Estrogen receptor and/or progesterone receptor-positive breast cancer

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal, defined by 1 of the following criteria:

• Age > 55 years with cessation of menses
• Age ≤ 55 years with spontaneous cessation of menses for > 1 year
• Age ≤ 55 years with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND has postmenopausal estradiol levels
• Bilateral oophorectomy
• ECOG performance status 0-2
• Life expectancy ≥ 5 years
• WBC ≥ 3,000/mm³ OR granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Creatinine < 2.0 mg/dL
• Creatinine clearance ≥ 45 mL/min
• No hypercalcemia (i.e., calcium level > 1 mg/dL above ULN) OR hypocalcemia (i.e., calcium level > 0.5 mg/dL below lower limit of normal) within the past 6 months
• 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 nonmalignant systemic diseases, including any of the following:

• Uncontrolled infection
• Uncontrolled diabetes mellitus
• Uncontrolled thyroid dysfunction
• Disease affecting bone metabolism (hyperparathyroidism, hypercortisolism, Paget's disease, osteogenesis imperfecta)
• Malabsorption syndrome
• No uncontrolled seizure disorders associated with falls
• No known hypersensitivity to zoledronate or other bisphosphonates, letrozole, calcium, or vitamin D
• No concurrent active dental problems, including any of the following:

• Infection of the teeth or jawbone (maxillary or mandibular)
• Dental or fixture trauma
• Prior or current diagnosis of osteonecrosis of the jaw
• Exposed bone in the mouth
• Slow healing after dental procedures
• No contraindication to spine dual energy x-ray absorptiometry (DXA) as defined by any of the following:

• History of surgery at the lumbosacral spine, with or without implantable devices
• Scoliosis with a Cobb angle > 15 degrees at the lumbar spine
• Immobility, hyperostosis, or sclerotic changes at the lumbar spine, or evidence of sclerotic abdominal aorta sufficient to interfere with DXA scan
• Disease of the spine that would preclude the proper acquisition of a lumbar spine DXA
• No condition that would preclude study follow-up or compliance
• No psychiatric illness that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

• More than 3 weeks since prior and no other concurrent oral bisphosphonates
• No prior intravenous bisphosphonates
• No prior aromatase inhibitor therapy
• More than 6 months since prior anabolic steroids or growth hormone
• More than 2 weeks since prior and no concurrent inhibitor of osteoclastic bone resorption (e.g., calcitonin, mithramycin, or gallium nitrate)
• More than 30 days since prior systemic investigational drug and/or device
• More than 7 days since prior topical investigational drug
• More than 6 weeks since prior and no concurrent dental or jaw surgery (e.g., extraction, implants)
• Concurrent short-term corticosteroid therapy allowed
• No concurrent sodium fluoride, parathyroid hormone, or tibolone
• No other concurrent investigational drug or device