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A refined molecular taxonomy of breast cancer.

Abstract：

:The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER-/PR-/AR+ and one was triple negative (AR-/ER-/PR-). ERBB2-amplified tumors were split between the ER-/PR-/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer.

journal_name

Oncogene

journal_title

Oncogene

authors

Guedj M,Marisa L,de Reynies A,Orsetti B,Schiappa R,Bibeau F,MacGrogan G,Lerebours F,Finetti P,Longy M,Bertheau P,Bertrand F,Bonnet F,Martin AL,Feugeas JP,Bièche I,Lehmann-Che J,Lidereau R,Birnbaum D,Bertucci F,de

doi

10.1038/onc.2011.301

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

1196-206

issue

9

eissn

0950-9232

issn

1476-5594

pii

onc2011301

journal_volume

31

pub_type

杂志文章

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