title: Invasive breast cancer treated with taxol and epirubicin neo-adjuvant chemotherapy: the role in the outcome of the "crosstalk" between Erb receptors and p53.
abstract: OBJECTIVE
  To correlate p53 and ErbB receptors status with disease-free survival (DFS) and overall survival (OS) in locally advanced breast cancer.
  
  
  METHODS
  Sixty patients were included in a single-center, open-label, phase II trial (1998-2003). Analysis of Erb receptors and p53 status and estrogen receptor/progesterone receptor data were available for 33 patients. Neoadjuvant epirubicin 75 mg/m2 and paclitaxel 175-200 mg/m2 were administered every 21 days. The patients underwent surgery and radiation therapy and adjuvant chemo/hormonotherapy.
  
  
  RESULTS
  Approximately two thirds of the patients demonstrated overexpression of ErbB receptors and had mutant p53 overexpression. The disease recurred in 11/33 patients and 7 died (median follow-up 56 months). Detrimental effects on OS were established in cases of combined defective p53 expression and ErbB1-ErbB3 heterodimeric receptor overexpression. In contrast, normal p53 together with the same overexpressed heterodimeric combination of ErbB receptors showed no statistically significant effect.
  
  
  CONCLUSIONS
  In terms of the clinical impact of combinations of ErbB receptors with or without mutant p53, only the overexpressed various ErbB1-ErbB3 dimeric combinations and the ErbB1/ErbB2/ErbB3 triplet combination with mutated p53 were related to a significantly poorer outcome. This observation may help in the development of new strategies required for blocking these molecular pathways and improving the outcome of patients with locally advanced breast cancer.
authors.affiliation: Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Sarid
authors.forename: Ilan G
authors.initials: IG
authors.lastname: Ron
authors.forename: Lior
authors.initials: L
authors.lastname: Shoshan
authors.forename: Itai
authors.initials: I
authors.lastname: Barnea
authors.forename: Sima
authors.initials: S
authors.lastname: Shina
authors.forename: Mimi
authors.initials: M
authors.lastname: Baratz
authors.forename: Julia
authors.initials: J
authors.lastname: Greenberg
authors.forename: Ofer
authors.initials: O
authors.lastname: Merimsky
authors.forename: Rami
authors.initials: R
authors.lastname: Ben-Yosef
authors.forename: Shahar
authors.initials: S
authors.lastname: Lev-Ari
authors.forename: Yaffa
authors.initials: Y
authors.lastname: Keidar
authors.forename: Neora
authors.initials: N
authors.lastname: Yaal-Hahoshen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis / Q000378:metabolism*; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018739:Oncogene Proteins v-erbB; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53