Neo-Adjuvant Chemotherapy (TAC) With or Without Zoledronic Acid in Treating HER2-negative Breast Cancer Patients

OBJECTIVES:

Primary

• To determine the value of neoadjuvant chemotherapy comprising doxorubicin hydrochloride, cyclophosphamide, and docetaxel with or without zoledronic acid in patients with HER2-negative large resectable or locally advanced breast cancer.

Secondary

• To correlate clinical response with pathological responses in both treatment arms.
• To evaluate the disease-free survival and overall survival of patients treated with this regimen.
• To evaluate the safety and tolerability of adding zoledronic acid to neoadjuvant chemotherapy.
• To evaluate heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen.

OUTLINE: Patients are randomized between 2 treatment arms.

• Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Patients also receive zoledronic acid IV over 15 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV as in arm I. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Large resectable or locally advanced disease

• T2 (≥ 2 cm and positive lymph nodes), T2 (≥ 3 cm), ≥ T3, T4, any N, M0 disease
• Measurable disease (breast and/or lymph nodes)
• HER2-negative disease by core biopsy
• No evidence of distant metastases (M1)
• No prior breast cancer

PATIENT CHARACTERISTICS:

• Female
• Menopausal status unspecified
• WHO performance status 0-2
• Not pregnant or nursing
• WBC ≥ 3.0 x 10^9/L
• Neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Bilirubin ≤ 1.5 times upper limit of normal (UNL)
• ALT and/or AST ≤ 2.5 times UNL
• Alkaline phosphatase ≤ 5 times UNL
• Creatinine clearance ≥ 50 mL/min
• Accessible for treatment and follow-up
• No previous malignancy within the past 5 years except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
• No peripheral neuropathy > grade 2 (of any cause)
• No other serious diseases including recent myocardial infarction, clinical signs of cardiac failure, or clinically significant arrhythmias
• No poor dental health
• No known hypersensitivity reaction to any of the components of the treatment
• No medical or psychological condition that, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent

PRIOR CONCURRENT THERAPY:

• No prior breast surgery except for biopsy
• No prior chemotherapy or radiotherapy
• No prior bisphosphonates