HER-2 underexpression

Approximately 40 % of young women with luminal HER2-negative breast cancers have HER2-low or ultralow disease. These findings highlight the importance of accurately assessing HER2 expression in YWBC to identify candidates for emerging HER2-targeted therapies such as trastuzumab deruxtecan.

P=N/A, N=46, Not yet recruiting, The Affiliated Hospital of Inner Mongolia Medical University; The Affiliated Hospital of Inner Mongolia Medical University

P2, N=53, Not yet recruiting, The Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital); The Third Affiliated Hospital of Naval Me

P=N/A, N=300, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Moreover, our findings suggest that HER2 status could be a relevant prognostic marker in these malignancies. Traditional anti-HER2 targeted therapies are indicated for HER2-positive patients, while a broader population of patients with HER2-low expression may benefit from novel anti-HER2 antibody-drug conjugates.

Integrating the clinical experience of Chinese pathologists and oncologists, and following expert panel discussions, a consensus on the clinical diagnosis and treatment of HER-2-low and HER-2-ultralow breast cancer was developed. This consensus aims to deepen clinicians' understanding of HER-2-low and HER-2-ultralow breast cancer, promote more precise clinical decision-making, and ultimately improve patient survival and quality of life.

P2, N=249, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Our findings suggest that BCNST-MP tumors are rarely larger than 5 cm and are frequently lymph node-negative. Most patients were negative for ER, PR, AR, and HER2. Notably, HER2-low expression was observed in approximately 30% of cases, suggesting therapeutic implications.

This case highlights the potential efficacy and tolerability of T-DXd in men and challenges the systematic exclusion of male patients from clinical trials involving HER2-low mBC. We advocate routine HER2-low testing and gender-inclusive trial design.

Class-wise F1 scores were 75.6% for HER2-0, 82.4% for HER2-low, and 91.5% for HER2-high, indicating the challenge in distinguishing HER2-0 and HER2-low cases. This study highlights the potential of simple yet effective deep learning techniques to significantly improve accuracy and reproducibility in breast cancer classification, supporting their integration into clinical workflows for better patient outcomes.

P1, N=138, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Jun 2026

Our findings highlight triple negative HER2-low BC as a distinct subtype identifiable via standard immunohistochemistry, beyond just biomarker status. The study underscores the prognostic diversity among BC subtypes and emphasizes the importance of personalized treatment strategies.