title: Prognostic molecular markers and neoadjuvant therapy response in anthracycline-treated breast cancer patients.
abstract: BACKGROUND
  Identifying biomarkers that can predict the prognosis and treatment response is helpful for individualizing breast cancer (BC) therapy. A neoadjuvant treatment setting is ideal for testing biomarkers capable of predicting the treatment response. This study analyzed the value of immunohistochemical biomarkers for predicting pathological complete response (pCR) and prognosis in a group of BC patients receiving standardized treatment.
  
  
  METHODS
  A total of 100 BC patients were treated with neoadjuvant chemotherapy (four cycles of epirubicin and cyclophosphamide) between 2000 and 2005. Formalin-fixed and paraffin-embedded core biopsies were taken before chemotherapy for immunohistochemical staining of ER, PgR, HER2, Bcl-2, p53, cyclin D1, CK5/6, CK8, CK18, and TOP2A. Patient and tumor characteristics and biomarker scores were used to predict pCR and prognosis, using logistic regression and Cox proportional hazard models.
  
  
  RESULTS
  pCR was achieved in 11 patients and was predicted by the established marker Ki-67. In addition, CK5/6 and CK18 improved the prediction model and were associated with lower pCR rates. For the prognosis, only the established markers nodal status, Ki-67, and PgR predicted overall survival and nodal status; Ki-67 and PgR predicted distant disease-free survival.
  
  
  CONCLUSIONS
  In this small retrospective study, CK5/6 and CK18 appeared to improve prediction of pCR in addition to the established markers. CK5/6 may indicate a tumor type resembling a basal phenotype that is more resistant to anthracycline-based therapy, and CK18 may indicate a luminal subtype that is more resistant to chemotherapy. However, these results need to be replicated in larger studies.
authors.affiliation: Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: David L
authors.initials: DL
authors.lastname: Wachter
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Lothar
authors.initials: L
authors.lastname: Haeberle
authors.forename: Ruediger
authors.initials: R
authors.lastname: Schulz-Wendtland
authors.forename: Arno
authors.initials: A
authors.lastname: Dimmler
authors.forename: Thomas
authors.initials: T
authors.lastname: Koscheck
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Renner
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lux
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Rauh
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schrauder
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015251:Epirubicin; D003520:Cyclophosphamide