chemotherapy and/or hormone therapy with or without zoledronate in treating women with stage ii or stage iii breast cancer

Conditions: Breast Cancer; Metastatic Cancer

Summary: rationale: zoledronate may delay or prevent the formation of bone metastases. it is not yet known whether chemotherapy and/or hormone therapy are more effective with or without zoledronate in preventing cancer recurrence and bone metastases in women with breast cancer. purpose: this randomized phase iii trial is studying giving chemotherapy and/or hormone therapy together with zoledronate to see how well they work compared to chemotherapy and/or hormone therapy alone in preventing cancer recurrence and bone metastases in women with stage ii or stage iii breast cancer.

objectives: primary * compare disease-free survival of women with stage ii or iii breast cancer at high risk of relapse treated with neoadjuvant or adjuvant chemotherapy and/or hormonal therapy with vs without zoledronate. secondary * compare time to bone metastases, as first recurrence, in patients treated with these regimens. * compare time to bone metastases, per se, in patients treated with these regimens. * compare time to distant metastases in patients treated with these regimens. * compare overall survival in patients treated with these regimens. * compare the reduction in skeletal-related events (fractures, spinal cord compression, radiotherapy to the bone, surgery to the bone, and hypercalcemia) before and after the development of bone metastases in patients treated with these regimens. * determine the safety and toxicity of zoledronate in patients treated with these regimens. * correlate prognostic factors, such as estrogen-receptor and progesterone-receptor status, tnm stage, tumor grade, her2/neu status, and menopausal status with treatment outcome in patients treated with these regimens. * determine more specific prognostic indicators for the development of bone metastases and factors that are able to predict specific benefit from bisphosphonate treatment using proteomics, tissue micro-array, and other modern techniques in these patients. outline: this is a randomized, open-label, parallel-group, multicenter study. patients are stratified according to participating center. patients are randomized to 1 of 2 treatment arms. * arm i: patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy. patients also receive concurrent zoledronate iv over 15 minutes every 3-4 weeks for 6 doses, every 3 months for 8 doses, and then every 6 months for 5 doses in the absence of disease progression or unacceptable toxicity. * arm ii: patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy alone. after completion of study treatment, patients are followed annually for 5 years. projected accrual: a total of 3,300 patients (1,650 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria:
disease characteristics: * diagnosis of primary breast cancer, meeting 1 of the following staging criteria: * stage ii * stage iii * t stage ≥ t1 * receiving or scheduled to receive chemotherapy and/or endocrine therapy * for patients receiving neoadjuvant therapy * tumor \> 5 cm (t3), features of locally advanced disease (t4), or biopsy-proven lymph node involvement (n1) * scheduled to proceed to definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy * no more than 30 days between initiation of neoadjuvant therapy and start of study drug * for patients receiving adjuvant therapy * must have undergone complete primary tumor resection and treatment of axillary lymph nodes\* * must have lymph node involvement * no prior neoadjuvant therapy\*\* * no more than 60 days since prior definitive surgery note: \*patients whose treatment plan includes further primary tumor resection and/or treatment of the axillary lymph nodes (e.g., clearance or radiotherapy) with curative intent after completion of chemotherapy are eligible provided the treatment is completed within 9 months of study entry note: \*\*preoperative endocrine therapy with a duration of \< 30 days is not considered prior neoadjuvant therapy * no evidence of recurrent or metastatic disease * no history of breast cancer, except ductal carcinoma in situ or lobular carcinoma in situ * hormone receptor status: * not specified patient characteristics: age * 18 and over sex * female menopausal status * premenopausal or postmenopausal performance status * karnofsky 80-100% or * ecog 0-1 life expectancy * not specified hematopoietic * not specified hepatic * not specified renal * creatinine ≤ 1.5 times upper limit of normal other * not pregnant or nursing * fertile patients must use effective contraception * no active dental problems, including dental abscess or infection of the jaw bone (e.g., maxilla or mandible) * no prior or current diagnosis of osteonecrosis of the jaw * no other malignancy within the past 5 years (including prior contralateral breast cancer) except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix * no history of disease with influence on bone metabolism, including any of the following: * paget's disease of the bone * primary hyperparathyroidism * osteoporosis requiring treatment or likely to require treatment within the next 6 months * no other severe physical or psychological disease that would preclude study compliance * no known hypersensitivity to bisphosphonates prior concurrent therapy: chemotherapy * see disease characteristics endocrine therapy * see disease characteristics radiotherapy * see disease characteristics surgery * see disease characteristics * more than 4 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants) * dental fillings, teeth scaling and polishing, or minor gingival surgery within the past 4 weeks are allowed other * more than 1 year since prior bisphosphonates * more than 30 days since prior investigational drugs * no concurrent investigational drugs (i.e., not locally approved for any indication)

Keywords: bone metastases stage ii breast cancer stage iiia breast cancer stage iiib breast cancer stage iiic breast cancer