TEST:

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

Combining palbociclib, trastuzumab, and ET was safe and improved significantly PFS, compared to TPC in previously treated HER2-positive, PAM50 luminal A/B ABC patients.

ERpHER2n-Basal breast cancer represents a clinically high-risk subgroup whose molecular resemblance to TNBC highlights potential therapeutic opportunities, particularly for immunotherapy and DNA repair-targeting treatments.

Basal-like PAM50 intrinsic subtype, limited prior exposure to chemotherapy and intrinsic sensitivity to the TOP1i irinotecan were associated with long-term response. Long-term responders exhibited persistent DNA damage and lacked early transcriptional activation of the G2/M cell cycle checkpoint that allow for DNA repair and RNA-DNA hybrid (R-loop) resolution, in parallel resulting in immune pathways transcriptional activation. Notably, characteristics linked to long-term response were primarily associated with the TOP1i payload activity.

Baseline characteristics indicative of reduced hormonal signaling and non-luminal tumor biology assessed more precisely using mRNA profiling can guide optimal tailoring of NACT for patients with high-risk HR+/HER2-tumors. Baseline molecular biology did not predict surgical outcomes following NACT.

To further improve the efficiency of the algorithm, we propose a stepwise model learning strategy combined with an approximation method for the posterior distribution. To validate the effectiveness of our approach, we finally apply it in various simulation studies as well as in a practical application involving the PAM50 gene expression data set.

P2, N=324, Active, not recruiting, NRG Oncology | Trial primary completion date: Mar 2026 --> Mar 2025

Multi-gene expression assays have reshaped precision oncology in breast cancer by enabling more individualized therapy and supporting de-escalation strategies. Future integration with multi-omics data, development of novel predictive assays, and expansion of validation in diverse populations are essential to maximize their global clinical utility.

P2, N=43, Recruiting, Medical University of South Carolina | Not yet recruiting --> Recruiting | Trial completion date: Jun 2028 --> Oct 2028 | Trial primary completion date: Jun 2027 --> Oct 2027

In routine practice, a short course of preoperative ET yields substantial reductions in tumor proliferation. Early assessment of Ki67 suppression offers a readily accessible indicator of endocrine sensitivity, and achieving CCCA identifies patients who have a more favorable prognosis and thus are potentially eligible to de-escalate in treatment strategies.

Overall, these results suggest that LRR-PCa has a distinct genomic and transcriptomic landscape from de novo prostate cancer. Specifically, LRR-PCa has an enrichment in SNVs in genes associated with tumor aggressiveness and/or DNA repair, has higher Decipher scores, a more basal subtype, and has transcriptomic evidence of lower androgen receptor activity and loss of tumor suppressor genes.

This study established a transcriptomic heterogeneity-resilient prognostic model for TNBC, enabling precise survival stratification and immune microenvironment assessment. The integrative nomogram and risk-guided therapeutic predictions address clinical challenges in TNBC management, advancing personalized treatment strategies.