title: Prognostic and predictive value of Phospho-p44/42 and pAKT in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.
abstract: BACKGROUND
  To evaluate the predictive and prognostic value of various molecular factors associated with the Ras/MAPK and PI3K/Akt signaling pathways in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy (NAC).
  
  
  METHODS
  A total of 113 patients were recruited in this retrospective study. Core needle biopsies and excision samples were assessed through immunohistochemistry for various biomarkers, including IGF-1R, Phospho-p44/42, Ki67, pAKT, PTEN, p27, and cyclinD1. The changes in these biomarkers after NAC and their predictive and prognostic values were investigated.
  
  
  RESULTS
  Significant decreases in Ki67, Phospho-p44/42, and pAKT expression were observed after treatment (30.7% vs. 18.1%, 36.4% vs. 18.9%, and 35.1% vs. 16.4%, respectively). The decreases in Phospho-p44/42, pAKT, and Ki67 expression were strongly associated with the response to anthracycline treatment (P = 0.027, P = 0.031, and P = 0.008, respectively). In a multivariate survival analysis, Phospho-p44/42 expression after neoadjuvant chemotherapy and lymph node status were significant independent prognostic factors of both relapse-free survival and overall survival.
  
  
  CONCLUSIONS
  Reductions in Ki-67, Phospho-p44/42, and pAKT expression are related to the clinical response to anthracycline-based NAC in HER2-positive breast cancer patients. High pAKT expression prior to NAC had a better clinical response. Phospho-p44/42 expression and lymph node status after NAC could be useful for determining relapse-free survival and overall survival.
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, 399 Ling-Ling Road, 200032 Shanghai, People's Republic of China. fdhlyx@gmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.forename: Tianwen
authors.initials: T
authors.lastname: Chen
authors.forename: Canming
authors.initials: C
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D014747:Vinblastine; D000077235:Vinorelbine; C508053:ERBB2 protein, human