title: The prognostic value of Ki67 in systemically untreated patients with node-negative breast cancer.
abstract: OBJECTIVE
  To evaluate the utility of Ki67 as a prognostic marker in a series of patients with node-negative breast cancer untreated with adjuvant systemic therapy.
  
  
  METHODS
  The cohort consisted of 203 cases treated with breast conserving surgery and radiation only; median follow-up was 183 months (range 156-277 months). An immunohistochemical panel of oestrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)5/6 and Ki67 and human epidermal growth factor 2 in situ hybridization (HER2-ISH) was performed on the tumour samples. Ki67 scores were evaluable in 193/203 patients (95.1%). The primary outcome was breast cancer specific survival (BCSS).
  
  
  RESULTS
  Of the cohort, 29 (14.2%) died of breast cancer. A cut off of 10% separated tumours into a 'Ki67-low' (n=70) or 'Ki67-high' group (n=123). The breast cancer specific survival was 97.1% and 77.6% for Ki67-low and Ki67-high groups, respectively. Univariate analysis showed that in this lymph node-negative cohort, the predictors for BCSS were tumour size, Ki67, LVI, age and histological grade 3. Multivariable analysis showed that Ki67 index and lymphovascular space invasion were independent predictors of breast cancer death. To examine the utility of Ki67 in assignment of immunohistochemically molecular subtypes, cases were assigned into Luminal A (ER-positive, HER2-negative, Ki67 ≤14%), Luminal B (ER-positive, HER2-negative, Ki67 >14%) and triple negative (ER/PR-negative and HER2-negative, any Ki67). The 15-year breast cancer specific survival was 91.7%, 79.4% and 75.8%, respectively.
  
  
  CONCLUSIONS
  A statistically significant difference in breast cancer specific survival is seen in groups defined using Ki67 and receptor status, whereas histological grading was not a significant predictor of survival. Ki67 immunostaining provides prognostic information beyond traditionally assessed clinicopathological variables.
authors.affiliation: Westmead Breast Cancer Institute, Westmead Hospital, , Westmead, New South Wales, Australia.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Pathmanathan
authors.forename: Rosemary L
authors.initials: RL
authors.lastname: Balleine
authors.forename: Upali W
authors.initials: UW
authors.lastname: Jayasinghe
authors.forename: Kellie L
authors.initials: KL
authors.lastname: Bilinski
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Provan
authors.forename: Karen
authors.initials: K
authors.lastname: Byth
authors.forename: A Michael
authors.initials: AM
authors.lastname: Bilous
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Salisbury
authors.forename: John
authors.initials: J
authors.lastname: Boyages
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen
keywords: Breast Cancer; Breast Pathology; Immunocytochemistry; KI 67