TEST:

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

Comprehensive documentation, including a vignette and user manual, supports effective application, while a dedicated tools portal provides installation instructions, frequently asked questions, and updates. The package is accessible at https://CRAN.R-project.org/package=PCAPAM50, with additional resources available at https://www.wriwindber.org/tools-portal/pcapam50/.

This study uncovers both shared and ancestry-specific immunogenomic features of breast cancer, highlighting the role of ancestry and other biological features in shaping the tumor immune microenvironment. These findings re-emphasize the need for population-informed approaches in breast cancer immunotherapy and biomarker development, to ensure equitable precision oncology strategies across global populations.

The "immune+/replication+" showed sensitivity to pembrolizumab (OR = 10.192, p < 0.001) and veliparib/carboplatin (OR = 5.184, p = 0.006), while "immune-/replication-" responded poorly to pembrolizumab (OR = 0.086, p < 0.001). Additionally, "immune+/replication-" had the best distant recurrence-free survival (DRFS), whereas "immune-/replication+" had the worst (log-rank p = 6 × 10-4, HR = 5.45). By linking imaging heterogeneity directly to molecular subtypes and therapeutic response, this framework provides a robust, non-invasive surrogate for genomic profiling and a strategic tool for personalized neoadjuvant therapy selection.

Protein-protein interaction (STRING) analysis indicated that TGFB2 is associated with EGFR and MYC from the PAM50 breast cancer gene signature. These findings suggest that correlation of TGFB2-related markers could potentially complement the PAM50 signature in the assessment of OS prognosis in breast cancer patients, but further validation of the TGFB2/EGFR/MYC proteins in tumors is warranted.

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