Zoledronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy After Surgery For Early Stage Breast Cancer

RATIONALE: It is not yet known whether zoledronate is effective in preventing bone loss in premenopausal women who are receiving adjuvant chemotherapy after undergoing surgery for early stage breast cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate in preventing bone loss in premenopausal women who are receiving chemotherapy after surgery for early stage breast cancer.

OBJECTIVES:

* Compare the changes in bone mineral density (BMD) and bone turnover that occur in premenopausal women with resected early stage breast cancer during and after 6 months of adjuvant chemotherapy.
* Determine the factors that predict bone loss during chemotherapy, particularly induction of amenorrhea, type of chemotherapeutic regimen, glucocorticoid exposure, and baseline BMD, in these patients.
* Determine whether zoledronate prevents bone loss in these patients when given during and after adjuvant chemotherapy.
* Determine the effect of zoledronate on markers of bone turnover in these patients during and after adjuvant chemotherapy.
* Determine whether the effect on markers of bone turnover predicts response to zoledronate in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative), progesterone receptor status (positive vs negative), and adjuvant chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive zoledronate IV over 15 minutes on day 1.
* Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, treatment repeats every 3 months for up to 4 courses in the absence of disease progression. Patients also receive calcium and cholecalciferol (vitamin D) supplements daily.

Quality of life is assessed at baseline and at 6 and 12 months.

Patients are followed at 1 year.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of localized breast cancer

  * Stage I or II (T1-3, N0-2, M0)
* Planned adjuvant chemotherapy (after surgery) of at least 6 months in duration
* Hormone receptor status:

  * Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age

* 18 to 50

Sex

* Female

Menopausal status

* Premenopausal or perimenopausal

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Creatinine less than 2 mg/dL

Other

* No T score of less than 2.0 on bone mineral density (BMD)
* No fragility fracture
* No lumbar spine anatomy that would preclude accurate BMD measurement of a minimum of 3 lumbar vertebrae
* Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* Not specified

Radiotherapy

* No concurrent radiotherapy

Surgery

* See Disease Characteristics

Other

* At least 1 month since prior calcitonin
* At least 12 months since prior bisphosphonates given for more than 1 month duration
* No concurrent fluoride therapy (10 mg/day or more)
* No concurrent enrollment in another experimental drug study