Clinical trial NCT00107263 (phase 3, status: completed)
Conditions: breast cancer, osteoporosis
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, M81.6, Z82.62, Z13.820, M81.8, Z87.310, M81.0, M80.80XS
Drugs: letrozole, zoledronic acid
SMILES: N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N, OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O
Eligibility 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