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Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response.
Breast Cancer Res Treat. 2010 Jan; 119(1):119-26.BC

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 (TN(IHC)), HER2+(IHC) and Luminal(IHC) (ER+(IHC)/HER2-(IHC)). By using the intrinsic gene set defined by Hu et al. five molecular subtypes (Basal(mRNA), HER2+(mRNA), Luminal A(mRNA), Luminal B(mRNA) and Normal-like(mRNA)) 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 B(mRNA) 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 A(mRNA) and Luminal B(mRNA) 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 A(mRNA) and Luminal B(mRNA) groups. Molecular subtyping suggests the existence of a HER2+(IHC)/Luminal(mRNA) group that responds poorly to trastuzumab-based chemotherapy. For Luminal(IHC) and triple negative(IHC) tumors, further subdivision into molecular subgroups does not offer a clear advantage in treatment selection.

Authors+Show Affiliations

Department of Bioinformatics and Statistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. j.d.ronde@nki.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19669409

Citation

de Ronde, Jorma J., et al. "Concordance of Clinical and Molecular Breast Cancer Subtyping in the Context of Preoperative Chemotherapy Response." Breast Cancer Research and Treatment, vol. 119, no. 1, 2010, pp. 119-26.
de Ronde JJ, Hannemann J, Halfwerk H, et al. Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Res Treat. 2010;119(1):119-26.
de Ronde, J. J., Hannemann, J., Halfwerk, H., Mulder, L., Straver, M. E., Vrancken Peeters, M. J., Wesseling, J., van de Vijver, M., Wessels, L. F., & Rodenhuis, S. (2010). Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Research and Treatment, 119(1), 119-26. https://doi.org/10.1007/s10549-009-0499-6
de Ronde JJ, et al. Concordance of Clinical and Molecular Breast Cancer Subtyping in the Context of Preoperative Chemotherapy Response. Breast Cancer Res Treat. 2010;119(1):119-26. PubMed PMID: 19669409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. AU - de Ronde,Jorma J, AU - Hannemann,Juliane, AU - Halfwerk,Hans, AU - Mulder,Lennart, AU - Straver,Marieke E, AU - Vrancken Peeters,Marie-Jeanne T F D, AU - Wesseling,Jelle, AU - van de Vijver,Marc, AU - Wessels,Lodewyk F A, AU - Rodenhuis,Sjoerd, Y1 - 2009/08/08/ PY - 2009/06/02/received PY - 2009/07/25/accepted PY - 2009/8/12/entrez PY - 2009/8/12/pubmed PY - 2010/2/23/medline SP - 119 EP - 26 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 119 IS - 1 N2 - 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(IHC)), HER2+(IHC) and Luminal(IHC) (ER+(IHC)/HER2-(IHC)). By using the intrinsic gene set defined by Hu et al. five molecular subtypes (Basal(mRNA), HER2+(mRNA), Luminal A(mRNA), Luminal B(mRNA) and Normal-like(mRNA)) 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 B(mRNA) 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 A(mRNA) and Luminal B(mRNA) 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 A(mRNA) and Luminal B(mRNA) groups. Molecular subtyping suggests the existence of a HER2+(IHC)/Luminal(mRNA) group that responds poorly to trastuzumab-based chemotherapy. For Luminal(IHC) and triple negative(IHC) tumors, further subdivision into molecular subgroups does not offer a clear advantage in treatment selection. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/19669409/Concordance_of_clinical_and_molecular_breast_cancer_subtyping_in_the_context_of_preoperative_chemotherapy_response_ L2 - https://doi.org/10.1007/s10549-009-0499-6 DB - PRIME DP - Unbound Medicine ER -