High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy

Eur J Cancer. 2013 Oct;49(15):3083-92. doi: 10.1016/j.ejca.2013.05.007. Epub 2013 Jun 15.

Abstract

Aim: 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.

Concluding statement: 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.

Keywords: Axillary dissection; Axillary radiotherapy; Early breast cancer; Ki67.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Axilla / pathology
  • Axilla / radiation effects
  • Axilla / surgery
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Ki-67 Antigen / metabolism*
  • Lymph Nodes / pathology
  • Lymph Nodes / radiation effects
  • Lymph Nodes / surgery
  • Methotrexate / administration & dosage
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Tamoxifen / therapeutic use
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / radiotherapy
  • Triple Negative Breast Neoplasms / surgery

Substances

  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Fluorouracil
  • Methotrexate