Intervention: Zoledronic acid
Trial phase: Not Applicable
ATC code: M05BA08 | M05BB08
SMILES: O=P(O)(O)C(O)(Cn1ccnc1)P(=O)(O)O
Sex: Female
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 52
Group description: 4 mg intravenously over 15 minutes every 6 months (until disease progression or for 5 years)
Eligibility criteria:
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