Evaluation of Chemotherapy Prior to Surgery With or Without Zometa for Women With Locally Advanced Breast Cancer

• Drug: Zometa
  Other Name: Zoledronic acid
• Drug: Epirubicin
  Other Name: Ellence
• Drug: Docetaxel
  Other Name: Taxotere
• Drug: Trastuzumab
  ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH
  Other Name: Herceptin
• Radiation: External beam radiation
• Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

• Experimental: Zometa

  Zometa 4 mg IV every 3 weeks for a total of 17 doses. The first treatment will be given at the time of the first chemotherapy treatment and will continue for approximately 1 year.

  Neoadjuvant therapy

  • Epirubicin 75 mg/m2 IV every 21 days for 4 cycles prior to surgery
  • Docetaxel 75 mg/m2 IV every 21 days for 4 cycles prior to surgery

  Surgery - modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

  Adjuvant therapy

  • Epirubicin 75 mg/m2 IV every 21 days for 2 cycles
  • Docetaxel 75 mg/m2 IV every 21 days for 2 cycles
  • All patients who are found to be Her-2 overexpressing by 3+ by ICH for FSH will receive trastuzumab 6 mg/kg IV every 3 weeks for 1 year post surgery

  Radiation therapy - 50-60 Gy in 1.8-2.0 Gy daily fractions to the breast or chest wall. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks

  Interventions:

  • Drug: Zometa
  • Drug: Epirubicin
  • Drug: Docetaxel
  • Drug: Trastuzumab
  • Radiation: External beam radiation
  • Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection
• Active Comparator: No Zometa

  Neoadjuvant therapy

  • Epirubicin 75 mg/m2 IV every 21 days for 4 cycles prior to surgery
  • Docetaxel 75 mg/m2 IV every 21 days for 4 cycles prior to surgery

  Surgery - modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

  Adjuvant therapy

  • Epirubicin 75 mg/m2 IV every 21 days for 2 cycles
  • Docetaxel 75 mg/m2 IV every 21 days for 2 cycles
  • All patients who are found to be Her-2 overexpressing by 3+ by ICH for FSH will receive trastuzumab 6 mg/kg IV every 3 weeks for 1 year post surgery

  Radiation therapy - 50-60 Gy in 1.8-2.0 Gy daily fractions to the breast or chest wall. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks

  Interventions:

  • Drug: Epirubicin
  • Drug: Docetaxel
  • Drug: Trastuzumab
  • Radiation: External beam radiation
  • Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

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Inclusion Criteria:

• Newly diagnosed primary invasive ductal or invasive lobular breast adenocarcinoma
• Tumor classified as clinically large T2 (2-5 cm), T3, T4 or any T with N1, N2
• Prior malignancies: limited to curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated and now > 5 years disease free
• >= 18 years of age
• Normal left ventricular function by echocardiogram or radioventriculogram
• Karnofsky Performance >= 70

Exclusion Criteria:

• No evidence of distant metastasis present by CT, Bone scan, or physical exam
• If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions may be further clarified by additional testing such as PET or MRI
• No current treatment with Zometa or other bisphosphonates
• No serious functional disorders of the liver or kidneys:
• Serum Creatinine <=2
• ALT/AST/ALK Phos <= 1.5 x upper limit of institutional normal.
• Bili <= 1.5 x upper limit of institutional normal.
• Currently not pregnant

• Novartis
• Pfizer