Perturbation and stability of PAM50 subtyping in population-based primary invasive breast cancer.

ABSTRACT: PAM50 gene expression subtypes represent a cornerstone in the molecular classification of breast cancer and are included in risk prediction models to guide therapy. We aimed to illustrate the impact of included genes and biological processes on subtyping while considering a tumor's underlying clinical subgroup defined by ER, PR, and HER2 status. To do this we used a population-representative and clinically annotated early-stage breast tumor cohort of 6233 samples profiled by RNA sequencing and applied a perturbation strategy of excluding co-expressed genes (gene sets). We demonstrate how PAM50 nearest-centroid classification depends on biological processes present across, but also within, ER/PR/HER2 subgroups and PAM50 subtypes themselves. Our analysis highlights several key aspects of PAM

SUBMITTER: Veerla S 

PROVIDER: S-EPMC10587090 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature