title: Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer.
abstract: BACKGROUND
  Patients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy. However, the significance of chemotherapy for those with luminal tumours has decreased due to recent changes in treatment strategies. Thus, it is often difficult to determine whether we should recommend chemotherapy to such patients in clinical practice. We investigated Ki67 expression, as a means of predicting the responses of luminal HER2-negative breast cancer patients to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that would benefit from these treatments.
  
  
  METHODS
  We enrolled 114 luminal HER2-negative breast cancer patients undergoing surgery after NAC. Biomarkers were examined using biopsy specimens obtained prior to treatment, to avoid any chemotherapy-related effects. Chemotherapy effects were determined employing operative specimens and we defined pathological complete response (pCR) as invasive nest disappearance, based only on the primary breast tumour. We applied receiver operating characteristic curve analysis to data from our 114 patients, to investigate Ki67 expression as a predictor of pCR.
  
  
  RESULTS
  The pCR rate was significantly higher for tumours with high Ki67 expression (p < 0.01) and all patients who obtained pCR remained recurrence-free during the median 58-month observation period. We identified 35% as the Ki67 cut-off value which distinguishes those with a pCR from other cases. Another dataset, comprised of 196 patients with a median 29-month observation period, was recruited for validation. Disease-free survival was found to be significantly (p < 0.01) lower in the patients with tumours in which Ki67 expression was higher than 35%.
  
  
  CONCLUSIONS
  Our results raise the possibility of the luminal HER2-negative subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy, as evidenced by improved survival.
authors: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-0033 Tokyo, Japan. yoshiyahorimoto@hotmail.com.
authors: Yoshiya
authors: Y
authors: Horimoto
authors: Atsushi
authors: A
authors: Arakawa
authors: Masahiko
authors: M
authors: Tanabe
authors: Hiroshi
authors: H
authors: Sonoue
authors: Fumie
authors: F
authors: Igari
authors: Koji
authors: K
authors: Senuma
authors: Emi
authors: E
authors: Tokuda
authors: Hideo
authors: H
authors: Shimizu
authors: Taijiro
authors: T
authors: Kosaka
authors: Mitsue
authors: M
authors: Saito
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human