English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The PAM50 classifier is widely used for breast tumor intrinsic subtyping based on gene expression. Clinical subtyping, however, is based on immunohistochemistry assays of 3–4 biomarkers. Subtype calls by these two methods do not completely match even on comparable subtypes. Nevertheless, the estrogen receptor (ER)-balanced subset for gene-centering in PAM50 subtyping, is selected based on clinical ER status. Here we present a new method called Principle Component Analysis-based iterative PAM50 subtyping (PCA-PAM50) to perform intrinsic subtyping in ER status unbalanced cohorts. This method leverages PCA and iterative PAM50 calls to derive the gene expression-based ER status and a subsequent ER-balanced subset for gene centering. Applying PCA-PAM50 to three different breast cancer study cohorts, we observed improved consistency (by 6–9.3%) between intrinsic and clinical subtyping for all three cohorts. Particularly, a more aggressive subset of luminal A (LA) tumors as evidenced by higher  MKI67  gene expression and worse patient survival outcomes, were reclassified as luminal B (LB) increasing the LB subtype consistency with IHC by 25–49%. In conclusion, we show that PCA-PAM50 enhances the consistency of breast cancer intrinsic and clinical subtyping by reclassifying an aggressive subset of LA tumors into LB. PCA-PAM50 code is available at  ftp://ftp.wriwindber.org/ .

PCA-PAM50 improves consistency between breast cancer intrinsic and clinical subtyping reclassifying a subset of luminal A tumors as luminal B