title: The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  To compare the prognostic significance of proliferation, as assessed by Ki67 expression, in breast cancer before and after neoadjuvant chemotherapy.
  
  
  METHODS
  A retrospective search of a prospectively maintained clinical database was performed to identify patients treated with neoadjuvant chemotherapy at the Royal Marsden Hospital. The expression of Ki67 was assessed using immunohistochemistry in pre-therapy core-needle biopsy and post-therapy surgical excision specimens. The following factors were considered pre- and post-chemotherapy for their relationship with relapse-free and overall survival: age, menstrual status, T and N stage, pre-therapy operability, Ki67, ER, PgR, HER2, grade, histological subtype, vascular invasion, clinical response, chemotherapy regimen, type of surgery performed, adjuvant therapy, pathological tumour size and nodal involvement.
  
  
  RESULTS
  In a matched cohort of 103 patients, on multivariate analysis of relapse-free survival, post-therapy Ki67 was the only significant independent prognostic factor. On multivariate analysis for overall survival, both pre- and excision Ki67 were significant independent predictors but the latter showed a stronger prognostic impact. The highest and lowest tertiles of excision Ki67 had different prognosis for both 5-year relapse-free (27% vs. 77%) and overall (39% and 93%) survival. In a cohort of 284 patients with only excision samples, post-therapy Ki67 was a significant independent prognostic factor on multivariate analysis.
  
  
  CONCLUSIONS
  Post-chemotherapy Ki67 is a strong predictor of outcome for patients not achieving a pathological complete response.
authors.affiliation: Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
authors.forename: Ash
authors.initials: A
authors.lastname: Nerurkar
authors.forename: Marina
authors.initials: M
authors.lastname: Parton
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen