Claudin-low breast cancers: clinical, pathological, molecular and prognostic characterization

Molecular Cancer

Research

Patrice Viens¹  José Adelaide²  Arnaud Guille²  Daniel Birnbaum²  Pascal Finetti²  Max Chaffanet²  François Bertucci³  Renaud Sabatier³ 

[1] Department of Medical Oncology, Institut Paoli-Calmettes (IPC), Marseille, France;Faculté de Médecine, Université Aix-Marseille, Marseille, France;Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille, UMR1068 Inserm, Institut Paoli-Calmettes (IPC), Marseille, France;Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille, UMR1068 Inserm, Institut Paoli-Calmettes (IPC), Marseille, France;Department of Medical Oncology, Institut Paoli-Calmettes (IPC), Marseille, France;Faculté de Médecine, Université Aix-Marseille, Marseille, France;

关键词: Breast cancer;    Claudin-low;    Molecular profiling;    Prognosis;    Response to chemotherapy;   

DOI  :  10.1186/1476-4598-13-228

 received in 2014-04-08, accepted in 2014-09-22,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe lastly identified claudin-low (CL) subtype of breast cancer (BC) remains poorly described as compared to the other molecular subtypes. We provide a comprehensive characterization of the largest series of CL samples reported so far.MethodsFrom a data set of 5447 invasive BC profiled using DNA microarrays, we identified 673 CL samples (12,4%) that we describe comparatively to the other molecular subtypes at several levels: clinicopathological, genomic, transcriptional, survival, and response to chemotherapy.ResultsCL samples display profiles different from other subtypes. For example, they differ from basal tumors regarding the hormone receptor status, with a lower frequency of triple negative (TN) tumors (52% vs 76% for basal cases). Like basal tumors, they show high genomic instability with many gains and losses. At the transcriptional level, CL tumors are the most undifferentiated tumors along the mammary epithelial hierarchy. Compared to basal tumors, they show enrichment for epithelial-to-mesenchymal transition markers, immune response genes, and cancer stem cell–like features, and higher activity of estrogen receptor (ER), progesterone receptor (PR), EGFR, SRC and TGFβ pathways, but lower activity of MYC and PI3K pathways. The 5-year disease-free survival of CL cases (67%) and the rate of pathological complete response (pCR) to primary chemotherapy (32%) are close to those of poor-prognosis and good responder subtypes (basal and ERBB2-enriched). However, the prognostic features of CL tumors are closer to those observed in the whole BC series and in the luminal A subtype, including proliferation-related gene expression signatures (GES). Immunity-related GES valuable in basal breast cancers are not significant in CL tumors. By contrast, the GES predictive for pCR in CL tumors resemble more to those of basal and HER2-enriched tumors than to those of luminal A tumors.ConclusionsMany differences exist between CL and the other subtypes, notably basal. An unexpected finding concerns the relatively high numbers of ER-positive and non-TN tumors within CL subtype, suggesting a larger heterogeneity than in basal and luminal A subtypes.

【 授权许可】

Unknown   
© Sabatier et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.