CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicAdvancements in Targeted Neoadjuvant and Adjuvant Therapies for Drug-Resistant Breast CancersView all 6 articles
Pathological Complete Response Yet Early Brain Relapse in HER2-Positive Breast Cancer: A Case-Based Review
Provisionally accepted
- Mianyang Central Hospital, Mianyang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Despite advances in anti-HER2 therapies leading to high pathological complete response (pCR) rates, the blood-brain barrier (BBB) still shelters micrometastatic deposits, so intracranial relapse continues to pose a formidable therapeutic obstacle in HER2-positive breast cancer (BC). Understanding the mechanisms underlying early central nervous system (CNS) relapse and integrating BBB-penetrant strategies remain urgent unmet needs. We report a 60-year-old woman with HER2-positive, hormone receptor-negative breast cancer who achieved pCR after neoadjuvant docetaxel combined with trastuzumab and pertuzumab, followed by 12 months of maintenance trastuzumab and pertuzumab. Despite achieving pCR and comprehensive systemic control, the patient developed multifocal brain metastases two months after completing maintenance therapy, without extracranial recurrence.This case underscores the limitations of large-molecule monoclonal antibodies in preventing CNS recurrence due to poor BBB permeability, allowing dormant CNS-adapted clones to persist and later expand. Emerging CNS-active therapies, including small-molecule tyrosine kinase inhibitors (TKIs) such as tucatinib and next-generation antibody-drug conjugates (ADCs) like trastuzumab deruxtecan, have shown promising intracranial activity. In addition, advanced strategies such as intensified MRI surveillance, radiomics, liquid biopsy, focused ultrasound-mediated BBB disruption, nanoparticle delivery systems, and radionuclide therapy offer potential avenues for early identification and prevention of cerebral metastases.
Keywords: Blood-Brain Barrier, brain metastases, case report, HER2-positive breast cancer, Pathological complete response
Received: 18 Jul 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Feng, Tong, Zhang and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuanli He
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.