Purpose: The aim of this study is to determine clinical and histopathological  characteristics that  predict tumor  response to anthracycline-based  neoadjuvant  chemotherapy  in  operable locally advanced breast cancer. Patients  and  methods:  We studied primary  tumor  core tissue  biopsies  from 60 patients with operable locally advanced breast cancer. Patients  received anthracycline-based chemotherapy. The World Health Organization (WHO) criteria were used for staging and the Nottingham modification of Bloom & Richardson scoring system was used for tumor grading. Immunohistochemical   staining  for  ER,  PgR,  HER-2  and  Ki-67  was  performed.  Clinical , histopathological and immunohistochemical  characteristics were analyzed and correlated with pathological response to neoadjuvanty chemotherapy. Results: Mean patients' age was 50.8±9.2  years. Sixty five percent of patients were postmenopausal.  Ninety percent had infiltrating  ductal carcinoma; NOS.  Five percent, 25% and 70%  of patients had stage liB,  IliA  and liiB  disease  respectively. Fifty  five percent of tumors were high grade. Sixty five percent of cases received neoadjuvant chemotherapy (NCT) in the form of FAC while 15% received FEC ( doxorubicin  was replaced with epirubicin) and 20% received AC (without 5-jiurouracil). Disease progression was recorded in 15% of patients while stable disease was observed in 25% of patients and 55% recorded partial response. Only 5% ofpatients concurred complete response. Breast conservative surgery (BCS) was conducted in 33.3% of responders to NCT (p 0.00). Factors associated with a better tumor response were younger age (p 0.03), smaller tumor size (p 0.01), lower nodal stage (p 0.00), high pathological grade (p 0.025), high Ki-67 labeling index, (p 0.00) and low expression of ER, PgR and Her2 (p 0.00). There was no significant relation between tumor response and each of menopausal status, tumor  stage, histological  type, presence of lymphovascular  space invasion (LVSI) or serum levels of tumor markers [CA15.3 & CEA]. Conclusion: Operable, locally advanced breast cancer with large tumor size, higher nodal stage, positive immunohistochemical  reaction to ER, PgR & Her2, lower Ki-67 labeling index and a lower tumor grade predict a lower response to anthracycline-based  NCT  These patients could alternatively benefit from radical resection or a different line of NCT to obtain a better response with the possibility of BCS.