HER-2 positive

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Dec 2025 --> May 2026

P2, N=37, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

This evolving landscape challenges the traditional use of HER2 as a diagnostic marker and underscores the need for a deeper understanding of HER2 biology. This review addresses these complexities, focusing on the emerging HER2-Low and Ultralow subtypes, and evaluates the distinct therapeutic responses across the spectrum of HER2 expression in different BC subtypes.

TQB2440 showed equivalent efficacy, comparable safety, PK, and immunogenicity profiles to reference pertuzumab in the neoadjuvant treatment of patients with HER2-positive early or locally advanced breast cancer.

Emerging evidence indicates that sequential ADC use can be effective despite some cross-resistance, especially when distinct payload mechanisms are employed. Clinical use should consider payload type, timing, and breast cancer subtype, but toxicities remain critical for decision-making. Research providing insights into resistance mechanisms and biomarkers is needed for personalized approaches.

Patients with HR+ /HER2+ BC had lower risks of breast cancer-specific death and higher overall survival rates. Mast cells were enriched in the HR+ /HER2+ BC group, while plasma cells were more abundant in the HR-/HER2+ BC group.In conclusion, HER2+ BC patients benefit differently from current HER2-directed therapies, maybe partly due to the HR status and gene mutations, and they may provide potentially prognostic and predictive value and new treatment strategies for clinicians.

P3, N=920, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: May 2026 --> Jul 2027 | Trial primary completion date: Dec 2025 --> Jul 2026

Dormancy was induced with low-dose FAC (5-Fluorouracil, Adriamycin, Cyclophosphamide). Notably, disseminated cell frequency inversely correlated with primary tumor size during neoadjuvant chemotherapy, underscoring the need for systemic therapies targeting distant dormant cells. These findings identify Bcl-xL as a central survival factor in chemotherapy-induced dormancy, and suggest that tumor-targeted systemic delivery of A-1331852 may eradicate disseminated dormant cells and prevent metastatic relapse in high-risk TNBC.

PD-1, PD-L1, CTLA-4, and HER2 positivity are associated with unfavorable clinical outcomes in SDC. Immune checkpoint regulator expression was comparable among AR/HER2 subtypes. PD-1, PD-L1, and CTLA-4 are potential therapeutic targets for SDC, particularly for the HER2/AR double-negative subtype.

This benefit was confirmed in a multivariable analysis, supporting PARPi as the preferred option in eligible patients. Our findings suggest that PARPi should be prioritized in the post-CDK4/6i treatment sequence for BRCA LP/PV carriers with HR+/HER2 aBC and highlight the critical role of germline BRCA testing.

Omission of SLNB in patients with small HR-positive/HER2-negative tumors results in a missed indication for CDK4/6i in <8 % with minimal impact on recurrence.