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

Jorma J. Ronde (1, 2) , Juliane Hannemann (2) , Hans Halfwerk (2) , Lennart Mulder (2) , Marieke E. Straver (3) , Marie-Jeanne T. F. D. Vrancken Peeters (3) , Jelle Wesseling (2) , Marc Vijver (2) , Lodewyk F. A. Wessels (1) , Sjoerd Rodenhuis (3)

1 Department of Bioinformatics and Statistics
2 Department Experimental Therapy
3 Department of Medical Oncology

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 (TN), HER2+ and Luminal (ER+/HER2−). By using the intrinsic gene set defined by Hu et al. five molecular subtypes (Basal, HER2+, Luminal A, Luminal B and Normal-like) 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+ group. 60% of the HER2+ tumors were not classified as HER2+. The HER2+/Luminal A or B group had a low response rate to a trastuzumab-chemotherapy combination with a pCR rate of 8%, while the HER2+ group had a pCR rate of 54%. The Luminal A and Luminal B groups showed similar degrees of response to chemotherapy. Neither the PR status nor the endocrine responsiveness index subdivided the ER+ tumors accurately into Luminal A and Luminal B groups. Molecular subtyping suggests the existence of a HER2+/Luminal group that responds poorly to trastuzumab-based chemotherapy. For Luminal and triple negative tumors, further subdivision into molecular subgroups does not offer a clear advantage in treatment selection.

Mots clés: Breast cancer subtypes; Intrinsic genes; Neoadjuvant chemotherapy response; Molecular subtypes; Clinical subtypes

Jorma J. Ronde, Juliane Hannemann, Hans Halfwerk, Lennart Mulder, Marieke E. Straver, et al.. Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Research and Treatment, 2009, 119 (1), pp.119-126. ⟨10.1007/s10549-009-0499-6⟩. ⟨hal-00535389⟩