title: Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment.
abstract: BACKGROUND
  The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer.
  
  
  METHODS
  Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible.
  
  
  RESULTS
  Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.
  
  
  CONCLUSIONS
  Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, California, USA. Peter.Fasching@uk-erlangen.de
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Katharina
authors.initials: K
authors.lastname: Heusinger
authors.forename: Lothar
authors.initials: L
authors.lastname: Haeberle
authors.forename: Melitta
authors.initials: M
authors.lastname: Niklos
authors.forename: Alexander
authors.initials: A
authors.lastname: Hein
authors.forename: Christian M
authors.initials: CM
authors.lastname: Bayer
authors.forename: Claudia
authors.initials: C
authors.lastname: Rauh
authors.forename: Ruediger
authors.initials: R
authors.lastname: Schulz-Wendtland
authors.forename: Mayada R
authors.initials: MR
authors.lastname: Bani
authors.forename: Michael
authors.initials: M
authors.lastname: Schrauder
authors.forename: Laura
authors.initials: L
authors.lastname: Kahmann
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lux
authors.forename: Johanna D
authors.initials: JD
authors.lastname: Strehl
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Arno
authors.initials: A
authors.lastname: Dimmler
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: David L
authors.initials: DL
authors.lastname: Wachter
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
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