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Aim: Brain metastasis remains a significant therapeutic challenge in HER2-positive breast cancer, contributing to poor prognosis and limited treatment options. This review aims to summarize recent advancements in targeted therapies for brain metastasis in HER2-positive breast cancer, with a focus on the efficacy, mechanisms, and clinical implications of antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs).
Methods: We conducted a comprehensive review of clinical trials, real-world studies, and preclinical research.
Main Content: This review summarizes the latest clinical and preclinical evidence on targeted therapies for brain metastasis in HER2-positive breast cancer. Key therapies, including trastuzumab deruxtecan (T-DXd) and tucatinib, are discussed, with a focus on their mechanisms, efficacy, and ability to overcome the blood-brain barrier (BBB). Clinical trials such as HER2CLIMB and DESTINY-Breast03, as well as real-world studies, are highlighted to demonstrate the superior intracranial response rates and survival benefits of these therapies.
Conclusion: ADCs and TKIs represent a paradigm shift in the management of brain metastases, offering new hope for patients with HER2-positive breast cancer. Future research should focus on optimizing combination therapies, exploring novel biomarkers, and addressing resistance mechanisms to further improve outcomes. This review underscores the importance of continued innovation in targeted therapies for brain metastasis.
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http://dx.doi.org/10.2147/BCTT.S503703 | DOI Listing |
ESMO Open
September 2025
Department of Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain; Clínic Barcelona
Background: Response to trastuzumab combined with chemotherapy (T-chemo) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) varies widely, highlighting the need for more precise biomarkers beyond conventional HER2 assessment with immunohistochemistry (IHC) and in situ hybridization (ISH). The HER2DX ERBB2 messenger RNA (mRNA) assay, a clinically validated genomic test initially developed for early-stage HER2-positive breast cancer, quantitatively measures ERBB2 expression and may improve patient selection for T-chemo in AGC.
Patients And Methods: In a retrospective cohort of 134 patients with AGC, including 58 who received T-chemo, we evaluated whether the HER2DX ERBB2 score defines more accurately HER2 status and correlates with treatment response and survival outcomes in HER2-positive AGC, compared with standard pathology-based methods.
Small Methods
September 2025
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
While human epidermal growth factor receptor (HER2) has emerged as a tumor-agnostic biomarker, standard HER2 testing for anti-HER2 therapies using immunohistochemistry (IHC) and in situ hybridization (ISH) assays remains subjective, time-consuming, and often inaccurate. To address these limitations, an ultrafast and precise HER2 testing method is developed using Lab-On-An-Array (LOAA) digital real-time PCR (drPCR), a fully automated digital PCR enabling real-time absolute quantification. A multicenter study involving four independent breast cancer cohorts cross-validates the high diagnostic accuracy of drPCR-based HER2 assessment.
View Article and Find Full Text PDFJ Med Chem
September 2025
UMR 1100, Research Center for Respiratory Diseases (CEPR), Team Proteolytic enzymes and their pharmacological targeting in lung diseases, University of Tours, Inserm, F-37032 Tours, France.
The prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly improved with the advent of anti-HER2 therapies, especially antibody-drug conjugates (ADCs). In this field, ADCs, like trastuzumab deruxtecan (T-DXd), using camptothecin analogs, represent a promising strategy. However, T-DXd can induce resistance and serious adverse effects, potentially driven by a non-specific Fcγ receptor-mediated endocytosis.
View Article and Find Full Text PDFClin Biochem
September 2025
Department of Biochemistry, Azerbaijan Medical University, Baku, Azerbaijan. Electronic address:
Objective: Breast cancer (BC) remains a leading cause of morbidity and mortality among women globally. This study aims to investigate HER2 mutations in HER2-negative BC and evaluate the diagnostic potential of matrix metalloproteinases (MMP-7, MMP-9) and CYR61 as serum biomarkers.
Material And Methods: The study involved 74 women diagnosed with BC (HER2-positive: n = 33; HER2-negative: n = 33; triple negative: n = 8) and 25 healthy controls.
Curr Probl Cardiol
September 2025
Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, INDONESIA; Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya, INDONESIA. Electronic address:
HER2-targeted therapies have dramatically improved outcomes for patients with HER2-positive breast cancer, but their potential for cardiotoxicity remains a critical clinical concern. Early trials reported high rates of cardiac dysfunction, particularly with concomitant anthracycline use, prompting the development of intensive cardiac monitoring strategies. However, emerging evidence suggests that most cardiotoxic events are asymptomatic, reversible, and rarely require permanent treatment discontinuation, particularly with newer agents such as antibody-drug conjugates.
View Article and Find Full Text PDF