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Prognostic value of proliferation in invasive breast cancer: a review
  1. P J van Diest1,
  2. E van der Wall2,
  3. J P A Baak3
  1. 1Department of Pathology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands
  2. 2Division of Internal Medicine and Dermatology, University Medical Centre Utrecht
  3. 3University Medical Centre Utrecht, Utrecht, The Netherlands and Department of Pathology, SIR Hospital, Stavanger, Norway
  1. Correspondence to:
 Professor P J van Diest
 Department of Pathology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands;


Breast cancer is the leading cause of death among solid tumours in women, and its incidence is increasing in the West. Adjuvant chemotherapy and hormonal treatment improve survival but have potentially serious side effects, and are costly. Because adjuvant treatment should be given to high risk patients only, and traditional prognostic factors (lymph node status, tumour size) are insufficiently accurate, better predictors of high risk and treatment response are needed. Invasive breast cancer metastasises haematogenously very early on, so many breast cancer prognosticators are directly or indirectly related to proliferation. Although studies evaluating the role of individual proliferation regulating genes have greatly increased our knowledge of this complex process, the functional end result—cells dividing—has remained the most important prognostic factor. This article reviews the prognostic value of different proliferation assays in invasive breast cancer, and concludes that increased proliferation correlates strongly with poor prognosis, irrespective of the methodology used. Mitosis counting provides the most reproducible and independent prognostic value, and Ki67/MIB1 labelling and cyclin A index are promising alternatives that need methodological fine tuning.

  • BrdU, bromodeoxyuridine
  • MAI, mitotic activity index
  • McM, minichromosome maintenance
  • PCNA, proliferating cell nuclear antigen
  • breast cancer
  • proliferation
  • prognosis

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