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 Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The high intra- and inter-tumor heterogeneity of many types of cancers, including breast cancer (BC), poses great challenge to development of subtype-specific prognosis. In BC, the classification of tumors as either ERα+ (Luminal A and Luminal B), HER2+ (ERα+ or ERα-) or triple-negative (TNBC)(Basal-like, claudin-low) guides both prognostication and therapy. Indeed, prognostic signatures for ERα+ BC are being incorporated into clinical use. However, these signatures distinguish between luminal A (low risk) and Luminal B (high risk) BC; signatures that identify low/high risk patients with luminal B BC are yet to be developed. Likewise, no signature is in clinical use for HER2+ or TNBC. The major obstacles to development of robust signatures stem from diversity of BC, clonal evolution and heterogeneity within each subtype. We have recently generated a prognostic signature for HER2+:ERα- BC based on the identification of genes that were differentially expressed in a tumor-initiating cell (TIC)-enriched fraction versus non-TIC fraction from a mouse model of HER2+ BC (MMTV-Hers/Neu). Here we describe the rationale behind development of this prognosticator, and present new features of the signature, including elevated PI3K pathway activity and low TNFalpha and IFNgamma signaling in high-risk tumors. In addition, we address controversies in the field such as whether random gene expression signatures significantly associate with cancer outcome. Finally, we suggest a guideline for development of prognostic signatures and discuss future directions.

A Tumor initiating cell-enriched prognostic signature for HER2+:ERα− breast cancer; rationale, new features, controversies and future directions