Breast Cancer Research and Treatment

, Volume 119, Issue 1, pp 119–126

Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response

  • Jorma J. de Ronde
  • Juliane Hannemann
  • Hans Halfwerk
  • Lennart Mulder
  • Marieke E. Straver
  • Marie-Jeanne T. F. D. Vrancken Peeters
  • Jelle Wesseling
  • Marc van de Vijver
  • Lodewyk F. A. Wessels
  • Sjoerd Rodenhuis
Clinical trial

DOI: 10.1007/s10549-009-0499-6

Cite this article as:
de Ronde, J.J., Hannemann, J., Halfwerk, H. et al. Breast Cancer Res Treat (2010) 119: 119. doi:10.1007/s10549-009-0499-6

Abstract

ER, PR and HER2 status in breast cancer are important markers for the selection of drug therapy. By immunohistochemistry (IHC), three major breast cancer subtypes can be distinguished: Triple negative (TNIHC), HER2+IHC and LuminalIHC (ER+IHC/HER2−IHC). By using the intrinsic gene set defined by Hu et al. five molecular subtypes (BasalmRNA, HER2+mRNA, Luminal AmRNA, Luminal BmRNA and Normal-likemRNA) can be defined. We studied the concordance between analogous subtypes and their prediction of response to neoadjuvant chemotherapy. We classified 195 breast tumors by both IHC and mRNA expression analysis of patients who received neoadjuvant treatment at the Netherlands Cancer institute for Stage II–III breast cancer between 2000 and 2007. The pathological complete remission (pCR) rate was used to assess chemotherapy response. The IHC and molecular subtypes showed high concordance with the exception of the HER2+IHC group. 60% of the HER2+IHC tumors were not classified as HER2+mRNA. The HER2+IHC/Luminal A or BmRNA group had a low response rate to a trastuzumab-chemotherapy combination with a pCR rate of 8%, while the HER2+mRNA group had a pCR rate of 54%. The Luminal AmRNA and Luminal BmRNA groups showed similar degrees of response to chemotherapy. Neither the PR status nor the endocrine responsiveness index subdivided the ER+IHC tumors accurately into Luminal AmRNA and Luminal BmRNA groups. Molecular subtyping suggests the existence of a HER2+IHC/LuminalmRNA group that responds poorly to trastuzumab-based chemotherapy. For LuminalIHC and triple negativeIHC tumors, further subdivision into molecular subgroups does not offer a clear advantage in treatment selection.

Keywords

Breast cancer subtypesIntrinsic genesNeoadjuvant chemotherapy responseMolecular subtypesClinical subtypes

Supplementary material

10549_2009_499_MOESM1_ESM.pdf (45 kb)
Supplementary material 1 (PDF 45 kb)
10549_2009_499_MOESM2_ESM.pdf (44 kb)
Supplementary material 2 (PDF 44 kb)
10549_2009_499_MOESM3_ESM.pdf (33 kb)
Supplementary material 3 (PDF 32 kb)

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jorma J. de Ronde
    • 1
    • 3
  • Juliane Hannemann
    • 3
  • Hans Halfwerk
    • 3
  • Lennart Mulder
    • 3
  • Marieke E. Straver
    • 2
  • Marie-Jeanne T. F. D. Vrancken Peeters
    • 2
  • Jelle Wesseling
    • 3
  • Marc van de Vijver
    • 3
  • Lodewyk F. A. Wessels
    • 1
  • Sjoerd Rodenhuis
    • 2
  1. 1.Department of Bioinformatics and StatisticsThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Medical OncologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Department Experimental TherapyThe Netherlands Cancer InstituteAmsterdamThe Netherlands