title: Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy.
abstract: BACKGROUND
  Tumour expression of cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), erythroblastic leukaemia viral oncogene homologue-2 (ErbB2), Ki-67 and p53 in breast cancer are associated with poorer outcomes. We investigated in vivo changes of these proteins with neoadjuvant chemotherapy.
  
  
  METHODS
  Four core biopsies were taken from 100 breast cancer patients at baseline, during and upon completion of neoadjuvant chemotherapy. Immunohistochemical expression of these proteins were evaluated and correlated with clinicopathological features, clinical response and progression-free survival (PFS).
  
  
  RESULTS
  There was a statistically significant change from positivity to negativity in COX-2 expression with chemotherapy (P = 0.002), predominantly in clinical responders (P = 0.002). COX-2-positive tumours that remained positive had shorter PFS than those that turned negative. Estrogen receptor (ER)+ and COX-2+ tumours at baseline that remained COX-2+ fared worse than those that became COX-2 negative (PFS 27 versus 52 months, P = 0.002). No significant changes in IHC expression were observed for ER, progesterone receptor, ErbB2, EGFR, p53 or Ki67.
  
  
  CONCLUSIONS
  Chemotherapy induced change in COX-2 expression from positivity to negativity predominantly among clinical responders and is associated with longer PFS. Interaction between COX-2 and ER was observed, suggesting that some hormone receptor-positive patients may benefit from combining COX-2 inhibition with hormonal therapy.
authors.affiliation: Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: B Y S
authors.initials: BY
authors.lastname: Chuah
authors.forename: T
authors.initials: T
authors.lastname: Putti
authors.forename: M
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: A
authors.initials: A
authors.lastname: Charlton
authors.forename: P
authors.initials: P
authors.lastname: Iau
authors.forename: S A
authors.initials: SA
authors.lastname: Buhari
authors.forename: C I
authors.initials: CI
authors.lastname: Wong
authors.forename: S H
authors.initials: SH
authors.lastname: Tan
authors.forename: A L A
authors.initials: AL
authors.lastname: Wong
authors.forename: C W
authors.initials: CW
authors.lastname: Chan
authors.forename: B C
authors.initials: BC
authors.lastname: Goh
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C496540:PTGS2 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human