Review

Breast Cancer Research and Treatment

, Volume 115, Issue 2, pp 241-254

First online:

Proliferation is the strongest prognosticator in node-negative breast cancer: significance, error sources, alternatives and comparison with molecular prognostic markers

  • Jan P. A. BaakAffiliated withDepartment of Pathology, Stavanger University HospitalThe Gade Institute, University of BergenFree University Email author 
  • , Einar GudlaugssonAffiliated withDepartment of Pathology, Stavanger University HospitalThe Gade Institute, University of Bergen
  • , Ivar SkalandAffiliated withDepartment of Pathology, Stavanger University HospitalThe Gade Institute, University of Bergen
  • , Lydia Hui Ru GuoAffiliated withDepartment of Oncology-3, Longhua Hospital
  • , Jan KlosAffiliated withDepartment of Pathology, Stavanger University Hospital
  • , Tone Hoel LendeAffiliated withDepartment of Endocrine Surgery, Stavanger University Hospital
  • , Håvard SøilandAffiliated withDepartment of Endocrine Surgery, Stavanger University Hospital
  • , Emiel A. M. JanssenAffiliated withDepartment of Pathology, Stavanger University Hospital
  • , Axel zur HausenAffiliated withInstitute of Pathology, University Hospital Freiburg

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Abstract

Independent studies have shown that in node negative breast cancer patients less than 71 years, the proliferation marker mitotic activity index (MAI) is the strongest, most well reproducible prognosticator and chemotherapy success predictor. The MAI overshadows the prognostic value of tubule formation, nuclear atypia and thereby grade. An often used crude mitotic impression is much less prognostic than the MAI; strict adherence to the MAI protocol is therefore important. The prognostic value of the MAI is age dependent: although patients with a MAI ≥ 10 always have a poor prognosis irrespective of age, a low MAI (<10) loses its favourable prognostic association in women >70 years. PPH3 counts are prognostically stronger than the MAI, and markers such as Cyclin-B and E2FR are promising, but must be validated. Compared with commercial prognostic gene expression signatures, the MAI is at least as strong prognostically, has far fewer false positive results and as such should be included as an independent feature in any node negative breast cancer pathology report.

Keywords

Breast cancer Proliferation Mitotic activity index Prognosis Error sources Molecular markers