title: HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination.
abstract: BACKGROUND
  Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting.
  
  
  METHODS
  Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis.
  
  
  RESULTS
  Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis.
  
  
  CONCLUSIONS
  Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination.
authors.affiliation: Department of Gynecology and Obstetrics, Breast Disease Division, Ribeirao Preto School of Medicine, HCFMRP-USP, Ribeirão Preto, São Paulo, Brazil. daniel.tiezzi@yahoo.com
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tiezzi
authors.forename: Jurandyr M
authors.initials: JM
authors.lastname: Andrade
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-Silva
authors.forename: Fábio E
authors.initials: FE
authors.lastname: Zola
authors.forename: Heitor R C
authors.initials: HR
authors.lastname: Marana
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Tiezzi
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D000077143:Docetaxel; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human