title: Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response.
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: Department of Bioinformatics and Statistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. j.d.ronde@nki.nl
authors: Jorma J
authors: JJ
authors: de Ronde
authors: Juliane
authors: J
authors: Hannemann
authors: Hans
authors: H
authors: Halfwerk
authors: Lennart
authors: L
authors: Mulder
authors: Marieke E
authors: ME
authors: Straver
authors: Marie-Jeanne T F D
authors: MJ
authors: Vrancken Peeters
authors: Jelle
authors: J
authors: Wesseling
authors: Marc
authors: M
authors: van de Vijver
authors: Lodewyk F A
authors: LF
authors: Wessels
authors: Sjoerd
authors: S
authors: Rodenhuis
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D008957:Models, Genetic; D057234:Preoperative Period; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone