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Loi, Sherene; Haibe-Kains, Benjamin; Desmedt, Christine; Lallemand, Françoise; Tutt, Andrew M; Gillet, Cheryl; Ellis, Paul; Harris, Adrian; Bergh, Jonas; Foekens, John A; Klijn, Jan G M; Larsimont, Denis; Buyse, Marc; Bontempi, Gianluca; Delorenzi, Mauro; Piccart, Martine J; Sotiriou, Christos
Journal of clinical oncology, 04/2007, Letnik: 25, Številka: 10Journal Article
A number of microarray studies have reported distinct molecular profiles of breast cancers (BC), such as basal-like, ErbB2-like, and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER) -positive subtypes has been inconsistent. Therefore, refinement of their molecular definition is needed. We have previously reported a gene expression grade index (GGI), which defines histologic grade based on gene expression profiles. Using this algorithm, we assigned ER-positive BC to either high-or low-genomic grade subgroups and compared these with previously reported ER-positive molecular classifications. As further validation, we classified 666 ER-positive samples into subtypes and assessed their clinical outcome. Two ER-positive molecular subgroups (high and low genomic grade) could be defined using the GGI. Despite tracking a single biologic pathway, these were highly comparable to the previously described luminal A and B classification and significantly correlated to the risk groups produced using the 21-gene recurrence score. The two subtypes were associated with statistically distinct clinical outcome in both systemically untreated and tamoxifen-treated populations. The use of genomic grade can identify two clinically distinct ER-positive molecular subtypes in a simple and highly reproducible manner across multiple data sets. This study emphasizes the important role of proliferation-related genes in predicting prognosis in ER-positive BC.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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