title: High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy.
abstract: OBJECTIVE
  Axillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ≤1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up.
  
  
  METHODS
  We retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling.
  
  
  RESULTS
  Only 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p=0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p=0.001). Ten-year DFS for high (≥14%) Ki67 cancers was lower than for low Ki67 cancers (p=0.027); however, this effect was mainly confined to the no axillary radiotherapy arm.
  
  
  CONCLUSIONS
  For patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.
authors.affiliation: Division of Senology, European Institute of Oncology, Milan, Italy; University of Milan, School of Medicine, Milan, Italy. Electronic address: stefano.zurrida@ieo.it.
authors.forename: S
authors.initials: S
authors.lastname: Zurrida
authors.forename: V
authors.initials: V
authors.lastname: Bagnardi
authors.forename: G
authors.initials: G
authors.lastname: Curigliano
authors.forename: M G
authors.initials: MG
authors.lastname: Mastropasqua
authors.forename: R
authors.initials: R
authors.lastname: Orecchia
authors.forename: D
authors.initials: D
authors.lastname: Disalvatore
authors.forename: M
authors.initials: M
authors.lastname: Greco
authors.forename: L
authors.initials: L
authors.lastname: Cataliotti
authors.forename: G
authors.initials: G
authors.lastname: D'Aiuto
authors.forename: N
authors.initials: N
authors.lastname: Talakhadze
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: G
authors.initials: G
authors.lastname: Viale
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001365:Axilla / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D019394:Ki-67 Antigen; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human
keywords: Axillary dissection; Axillary radiotherapy; Early breast cancer; Ki67