title: Ki-67 evaluation at the hottest spot predicts clinical outcome of patients with hormone receptor-positive/HER2-negative breast cancer treated with adjuvant tamoxifen monotherapy.
abstract: BACKGROUND
  The clinicopathological importance of Ki-67 in breast cancers has been intensely studied; however, there have been few systematic large studies of patients treated with predefined adjuvant therapy. Further, Ki-67 evaluation methodology differed among studies, which prevents Ki-67 from being used for clinical practice. We performed a large systematic study using routinely processed tissues and compared various scoring methods.
  
  
  METHODS
  Representative slides of archival tissue blocks of 442 consecutive invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and having a long follow-up period were subjected to immunohistochemistry using anti-Ki-67 monoclonal antibody, Mib-1. Both the average score across the section and the score at the hottest spot were assessed.
  
  
  RESULTS
  Ki-67 evaluated at the hottest spot, not the average score across the section, independently predicted poor clinical outcomes of patients with hormone receptor-positive/HER2-negative cancer. Ki-67 was not a predictor of clinical outcome in patients with triple-negative breast cancer. Overall, high Ki-67 level significantly correlated with classic unfavorable clinicopathological factors, correlating negatively with the status of estrogen receptor (ER)-α and progesterone receptor (PR), and positively with HER2 status and grade. ER-β status positively correlated with the Ki-67 level.
  
  
  CONCLUSIONS
  Ki-67 evaluation at the hottest spot was superior to that determined by average score across the section as a predictor of outcome in patients with hormone receptor-positive/HER2-negative breast cancers treated with endocrine monotherapy. The different result obtained in patients with triple-negative carcinomas needs to be further investigated.
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan, nhonma@tmig.or.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Honma
authors.forename: Rie
authors.initials: R
authors.lastname: Horii
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Mamoun
authors.initials: M
authors.lastname: Younes
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D002277:Carcinoma / Q000737:chemistry* / Q000188:drug therapy; D017024:Chemotherapy, Adjuvant; D047629:Estrogen Receptor beta / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human