T-DXd showed remarkable preclinical activity against HER2 FISH-negative, IHC-low EEC both in-vitro and in-vivo. These findings support its use beyond HER2-high expression and may represent a novel and effective treatment option for patients with HER2-low EEC who have progressed on standard chemotherapy and immunotherapy.

P=N/A, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026

P2, N=36, Not yet recruiting, Laura Huppert, MD, BA | Trial completion date: Mar 2029 --> Jun 2029 | Trial primary completion date: Mar 2029 --> Jun 2029

P2, N=42, Recruiting, Gruppo Oncologico del Nord-Ovest

P2, N=258, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Active, not recruiting --> Recruiting | N=76 --> 258 | Trial completion date: Jul 2026 --> Dec 2027 | Trial primary completion date: Apr 2025 --> Dec 2027

This classification (refined in ProMisE and TransPORTEC) enables precise treatment: immunotherapy (pembrolizumab, dostarlimab) works excellently in dMMR/MSI-H tumors, PI3K/AKT/mTOR inhibitors and trastuzumab deruxtecan in selected molecular subtypes, and hormone therapy in ER-positive tumors. Integrating the molecular profile with FIGO allows for truly personalized treatment, although MMRp/MSS tumors remain a challenge. The future lies in multi-omics, new biomarkers, and combination therapies.

The present study aimed to investigate the image-derived biodistribution, tolerability, and efficacy of [161Tb]Tb-trastuzumab as a potential therapeutic alternative or supplement to trastuzumab and trastuzumab deruxtecan in HER2-expressing tumors...Biodistribution of [161Tb]Tb-trastuzumab revealed high tumor uptake of more than 10 %ID/g of tissue, peaking at 72 h. [161Tb]Tb-trastuzumab in doses of up to 10 MBq was tolerated and highly effective at inhibiting tumor growth (P = 0.0007). These results support the potential of [161Tb]Tb-trastuzumab as an attractive treatment option for HER2-expressing cancers.

P3, N=0, Withdrawn, Danish Breast Cancer Cooperative Group | N=504 --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 Withdrawn | Trial primary completion date: May 2029 --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

This Delphi study found strong consensus on key concepts for sampling, pathological testing, interpretation, and reporting of HER2-low and ultralow breast cancer. While the opinions expressed align with current guidelines, more evidence on the clinicopathological implications is needed.

P3, N=506, Active, not recruiting, AstraZeneca | Trial completion date: Feb 2026 --> May 2026

For example, a PBAP-HER2 construct synergized with Herceptin and Kadcyla to eliminate human epidermal growth factor receptor 2 (HER2)-negative, PD-L1 positive cells. This work represents an innovative strategy for enhancing PD-L1-targeted therapies by leveraging pre-existing antibodies induced by vaccination or natural viral infections, alongside commercially available antibody-based therapies. Given the broad expression of PD-L1 across various solid tumors and hematologic malignancies, our strategy holds promise as a potentially widely applicable platform for diverse PD-L1-positive patient populations.