TEST:

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

Distinct integrated sirtuin scores thus capture subtype-specific metabolic/epigenetic states and provide robust RFS stratification across BC subtypes. These findings highlight sirtuins as integrators of longevity pathways and tumor metabolism, suggesting therapeutically exploitable vulnerabilities along NAD⁺-dependent regulatory axes.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i; palbociclib, ribociclib, abemaciclib, dalpiciclib) combined with endocrine therapy (ET) were a major advance in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) worldwide...However, clinical development of CDK4/6i in HER2+ MBC slowed, given the advent of highly effective tyrosine-kinase inhibitors (TKIs) (i.e., tucatinib) and antibody-drug conjugates (ADCs) (i.e., trastuzumab deruxtecan), which currently dominate the treatment armamentarium...Subsequently, the phase III PATINA trial (which included patients with 1L HR+HER2+ MBC, treated with palbociclib vs. placebo with maintenance ET+ H[P]) noted a striking PFS improvement of >15 months in the palbociclib arm, renewing interest in CDK4/6i-based treatments for HR+HER2+ MBC. Herein, we review the development of CDK4/6i in HER2+ BC, discussing current challenges and potential future directions.

Basal-like tumors harbor a distinct ferroptosis-associated transcriptional state linked to tumor aggressiveness and poor prognosis. These findings provide a biologically grounded framework for ferroptosis-related stratification and support future functional and translational studies targeting ferroptosis vulnerabilities in aggressive breast cancer.

P3, N=0, Withdrawn, Danish Breast Cancer Cooperative Group | N=504 --> 0 | Trial completion date: May 2029 --> Jan 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: May 2029 --> Jan 2026

RTN4IP1 expression was further linked to features of the tumor immune microenvironment and to differential responses to Tamoxifen and Paclitaxel; inhibition of RTN4IP1 was associated with greater drug sensitivity, while overexpression coincided with reduced response. Together, these findings indicate that RTN4IP1 is closely associated with BC progression, prognosis, and treatment response, supporting its potential relevance as a biomarker and a candidate target for further investigation.

Confusion matrices revealed significant improvements in distinguishing closely related subtypes such as Luminal A and Luminal B. Attention rollout provided interpretable heatmaps localizing discriminative histological regions associated with each subtype, aligning with established pathological criteria. This study demonstrates that integrating CTransPath-derived histology features with transcriptomic profiles through confidence-aware routing offers a practical, explainable, and computationally efficient approach for breast cancer subtype classification suitable for clinical decision support systems.

P=N/A, N=504, Recruiting, University Hospital Tuebingen | Trial primary completion date: Apr 2025 --> Apr 2027

P=N/A, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Dec 2026

P3, N=1156, Suspended, Alliance for Clinical Trials in Oncology | Recruiting --> Suspended

P2, N=23, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

P2, N=94, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P=N/A, N=200, Not yet recruiting, The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University