Effect of cross-platform gene-expression, computational methods on breast cancer subtyping in PALOMA-2 and PALLET studies

跨平台基因表达计算方法对PALOMA-2和PALLET研究中乳腺癌亚型的影响

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作者:Maggie Chon U Cheang ,Mothaffar Rimawi ,Stephen Johnston ,Samuel A Jacobs ,Judith Bliss ,Katherine Pogue-Geile ,Lucy Kilburn ,Zhou Zhu ,Eugene F Schuster ,Hui Xiao ,Lisa Swaim ,Shibing Deng ,Dongrui R Lu ,Eric Gauthier ,Jennifer Tursi ,Dennis J Slamon ,Hope S Rugo ,Richard S Finn ,Yuan Liu

Abstract

Intrinsic breast cancer molecular subtyping (IBCMS) provides significant prognostic information for patients with breast cancer and helps determine treatment. This study compared IBCMS methods on various gene-expression platforms in PALOMA-2 and PALLET trials. PALOMA-2 tumor samples were profiled using EdgeSeq and nanostring and subtyped with AIMS, PAM50, and research-use-only (ruo)Prosigna. PALLET tumor biopsies were profiled using mRNA sequencing and subtyped with AIMS and PAM50. In PALOMA-2 (n = 222), a 54% agreement was observed between results from AIMS and gold-standard ruoProsigna, with AIMS assigning 67% basal-like to HER2-enriched. In PALLET (n = 224), a 69% agreement was observed between results from PAM50 and AIMS. Different IBCMS methods may lead to different results and could misguide treatment selection; hence, a standardized clinical PAM50 assay and computational approach should be used.Trial number: NCT01740427.

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