Advances in Targeted Therapy for Brain Metastases in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer: A Focus on ADCs and TKIs.

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.