RATIONALE: Zoledronic acid may prevent bone loss and help prevent or lessen musculoskeletal symptoms in women receiving hormone therapy for breast cancer.

PURPOSE: This phase II trial is studying how well zoledronic acid works in preventing musculoskeletal symptoms in post-menopausal women with stage I, stage II, or stage III breast cancer receiving letrozole.

PRIMARY OBJECTIVES:

I. Percentage of women experiencing aromatase inhibitor associated musculoskeletal symptoms (AIMSS) at 1, 3, 6, and 12 months after bisphosphonate therapy, as compared to historical controls.

II. Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and 1, 3, 6 and 12 months, from baseline, among those receiving bisphosphonate, as compared to historical controls.

SECONDARY OBJECTIVES:

I. Change in pain scores on visual analog scale (VAS) at 1, 3, 6 and 12 months, from baseline, compared to historical controls.

II. Change in amount and/or frequency of oral analgesic use at 1, 3, 6 and 12 months from baseline among those receiving bisphosphonate therapy, as compared to historical controls.

III. Number of patients who discontinue or change aromatase inhibitor (AI) therapy.

IV. Change in menopausal symptoms (NSABP-revised), hot flash frequency (HFRDIS),sleep quality (PSQI), depression score (CESD) and overall quality of life (EuroQOL) in patients at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

V. Changes in plasma estrogen concentrations at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

VI. Change in bone mineral density (DEXA scan) at 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

VII. Change in bone turn over markers (serum-C telopeptide, bone-specific alkaline phosphatase, osteocalcin and urinary N-telopeptide) at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

VIII. Change in inflammatory markers (ESR, CRP, IL-1, IL-6, IL-8) at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

OUTLINE: Patients receive zoledronic acid intravenously (IV) at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria

• Patients with histologically proven DCIS or stage I-III invasive carcinoma of the breast that is estrogen and/or progesterone receptor positive by immunohistochemical staining who are considering aromatase inhibitor therapy; women may receive the AI on this study as initial adjuvant hormonal treatment or following tamoxifen; patients must have completed any adjuvant chemotherapy; patients may have received preoperative chemotherapy
• Postmenopausal status, defined as: >= 60 years of age; or < 60 years of age and amenorrheic for >= 12 months prior to day 1 if intact uterus/ovaries; or < 60 years of age, and the last menstrual period 6-12 months prior to day 1, if intact uterus/ovaries and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or < 60 years of age, without a uterus, and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or < 60 years of age and history of bilateral oophorectomy; or prior radiation castration with amenorrhea for at least 6 months; < 60 years of age and taking medication designed to suppress ovarian function and meets biochemical criteria for menopause (estradiol levels within institutional standards for postmenopausal status; women would have had to be taking the drug for at least 30 days prior to day 1)
• ECOG performance status 0-2
• Patient is aware of the nature of her diagnosis, understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form

Exclusion Criteria

• Concurrent use of hormone replacement therapy
• Concurrent use of tamoxifen; patients taking tamoxifen must discontinue the drug prior to first dose of zoledronic acid
• Concurrent use of other selective estrogen receptor modulator (SERM) such as raloxifene
• Concurrent consumption of soy supplements; routine dietary consumption of soy containing foods will be permitted
• Prior use of an aromatase inhibitor in any setting
• Current bisphosphonate use (oral or intravenous); prior bisphosphonate users would be eligible as long as the use was > 1 month ago for oral bisphosphonates and/or > 12 months ago for intravenous bisphosphonates, prior to starting study treatment
• Moderate to severe renal impairment (serum creatinine greater than 2 mg/dL or creatinine clearance less than 50 mL/min)
• Hypersensitivity to letrozole or zoledronic acid or any of its excipients
• Concomitant treatment with oral or intravenous corticosteroids
• Current active dental problems including infection or the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)