title: High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer.
abstract: BACKGROUND
  In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.
  
  
  METHODS
  We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).
  
  
  RESULTS
  A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤ 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤ 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.
  
  
  CONCLUSIONS
  Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.
  
  
  CONCLUSIONS
  The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.
authors.affiliation: Virgen de la Victoria University Hospital, Málaga, Spain ealbac@uma.es.
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
authors.affiliation: Valencia University Hospital, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.affiliation: Virgen de la Victoria University Hospital, Málaga, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Ribelles
authors.affiliation: Miguel Servet University Hospital, Zaragoza, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Anton-Torres
authors.affiliation: Jaén Hospital Complex, Jaen, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez-Rovira
authors.affiliation: Hospital del Mar Medical Research Institute-Institut Hospital del Mar d'Investigacions Mediques and Pompeu Fabra University, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: A Coruña University Hospital Complex, A Coruña, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Calvo
authors.affiliation: San Carlos University Hospial, Madrid, Spain.
authors.forename: Jose Antonio Lopez
authors.initials: JA
authors.lastname: García-Asenjo
authors.affiliation: Ramón y Cajal University Hospital, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Palacios
authors.affiliation: Virgen de la Salud Hospital, Toledo, Spain.
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Chacon
authors.affiliation: Valencian Institute of Oncology, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Biomedical Research Institute, Reina Sofía Hospital Complex, Córdoba, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: De la Haba-Rodriguez
authors.affiliation: Parc Taulí Health Corporation, Barcelona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Segui-Palmer
authors.affiliation: Germans Trias i Pujol University Hospital, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cirauqui
authors.affiliation: Germans Trias i Pujol University Hospital, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Margeli
authors.affiliation: Onkologikoa, Donostia, Spain.
authors.forename: Arrate
authors.initials: A
authors.lastname: Plazaola
authors.affiliation: Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Agusti
authors.initials: A
authors.lastname: Barnadas
authors.affiliation: GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Casas
authors.affiliation: GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Caballero
authors.affiliation: GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.affiliation: Fundación Jiménez Diaz University Hospital, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; Chemosensitivity; Ki67; Neoadjuvant chemotherapy; Predictive factor