TEST:

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

P2, N=976, Recruiting, MedSIR | Trial completion date: Dec 2028 --> Jun 2028 | Trial primary completion date: Dec 2028 --> Jun 2028

P3, N=5101, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2026 --> May 2030 | Trial primary completion date: May 2026 --> May 2030

Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.

The PAM50 basal-luminal subtyping shows promise as a molecular classification tool for predicting progression risk in PCa. This is one of the only prospective studies evaluating PAM50 subtyping for predicting cancer progression in a cohort of men undergoing AS for PCa.

P=N/A, N=1516, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Dec 2025 --> Dec 2026

P2/3, N=2270, Not yet recruiting, Unicancer

ERpHER2n HRD tumors show features of aggressive disease, but do not display a distinct transcriptional or DNA methylation profile that clearly differentiates them from HR-proficient tumors. Though numbers are limited, we present early evidence that HRD stratification by WGS could impact therapeutic strategies, as HRD BCs trended to poorer outcomes when not treated with chemotherapy.

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.