The purpose of this study is to evaluate the usual and the reverse sequence of an anthracycline followed by a taxane in locally advanced breast cancer.

Anthracylines and taxanes are the most active chemotherapy agents in the treatment of breast cancer. The usual sequence of an anthracycline followed by a taxane is due to the timing of their discovery and introduction in the treatment armamentarium. More recent evidence suggests that there is pre clinical as well as clinical rational for the reverse sequence.

The neoadjuvant approach allows quick evaluation of these different treatment strategies. At the same time, the study will collect tissue biopsies and blood at different time points in order to evaluate predictive biomarkers.

Inclusion Criteria:

1. Stage IIB to IIIB HER-2 negative breast cancer

2. ECOG performance status ≤ 2

3. Neuropathy grade <1 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0)

4. Adequate hematologic function with:

   • Absolute neutrophil count (ANC) >1500/μL
   • Platelets ≥100,000/μL
   • Hemoglobin ≥ 9 g/dL

5. Adequate hepatic and renal function with:

   • Serum bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x institutional ULN
   • Alkaline phosphatase ≤2.5 x institutional ULN
   • Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 50 mL/min

6. Adequate cardiac function

   • Left ventricular ejection fraction (LVEF) within institutional normal range

7. Knowledge of the investigational nature of the study and ability to provide consent for study participation

Exclusion criteria

1. Pregnancy
2. Bilateral, synchronous breast cancer
3. Previous diagnosis of breast or other cancer
4. Any other disease(s), psychiatric condition, metabolic dysfunction, that contraindicates the use of study drugs or that would make the patient inappropriate for this study