title: Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers.
abstract: BACKGROUND
  The criteria for classifying hormone receptor (HR)-positive/HER2-negative breast cancers into low-risk and high-risk subgroups remain undetermined. Supportive data for optimal criteria to identify tumors in the high-risk subgroup are necessary for Japanese patients with HR-positive/HER2-negative breast cancers.
  
  
  METHODS
  Using immunohistochemistry and fluorescence in situ hybridization, we identified 369 consecutive patients with HR-positive/HER2-negative, node-negative invasive breast cancers. We examined the prognostic impact of the Ki-67 labeling index (LI) based on 3 cutoff values, 10, 14, and 20 %, along with that of histological grade (HG) and nuclear grade (NG) by Cox's univariate and multivariate analyses.
  
  
  RESULTS
  The univariate analyses clearly showed that Ki-67 LI with any cutoff value divided the patients into distinct high-risk and low-risk groups, and that HG and NG were also powerful prognostic indicators. High Ki-67 LI with any cutoff value was strongly correlated with HG and NG, and when these parameters were included in the multivariate analyses, the impact of HG/NG was stronger than Ki-67 LIs. When the 10 % cutoff value was adopted, discordance between Ki-67 LI and grades was frequent in papillotubular-type invasive ductal carcinoma, predominantly intraductal carcinoma, and mucinous carcinoma.
  
  
  CONCLUSIONS
  Any of the Ki-67 LI values, regardless of cutoff value, could be applicable for the classification of high-risk and low-risk HR-positive/HER2-negative, node-negative invasive breast cancers. Luminal A/B subtyping according to Ki-67 LI, or HG/NG, in combination with histological type, appeared to be able to create an optimum risk estimation system for patients with HR-positive/HER2-negative, node-negative invasive breast cancers in Japan.
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan, makono@ncc.go.jp.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ono
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Mayu
authors.initials: M
authors.lastname: Yunokawa
authors.forename: Kan
authors.initials: K
authors.lastname: Yonemori
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimizu
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D044466:Asian People; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis* / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human