CNS Recurrence and the Expanding Role of ADCs in Breast Cancer

This section focuses on the relevance of central nervous system involvement in treatment planning and the emerging role of ADCs in intracranial disease. Dr Tarantino raises the question of whether systemic therapy can influence the risk of future brain metastasis. Historically, large antibody based molecules were not expected to demonstrate meaningful CNS activity due to limited entry into the brain. However, new clinical experience suggests that ADCs may overcome some of these limitations.

Dr Mouabbi discusses early signals from trastuzumab deruxtecan in patients with HER2 positive disease. He highlights evidence from DESTINY Breast 05 that indicates fewer CNS recurrences in the trastuzumab deruxtecan arm compared with TDM1, although recurrence was not eliminated. He notes that this observation is promising because CNS involvement in early stage disease often carries long term clinical consequences. He explains that patients may benefit from systemic therapy that can limit CNS spread even when the blood brain barrier is intact or partially disrupted.

The speakers also discuss activity associated with datopotamab deruxtecan and review observations from studies that included patients with active or stable brain metastasis. Although the mechanism behind ADC penetration into the CNS remains under investigation, the clinical patterns seen to date suggest that ADCs may provide meaningful benefit in selected patients.

The conversation highlights the importance of designing trials that directly evaluate intracranial endpoints. The experts note that future studies focused on CNS recurrence, CNS specific response, and leptomeningeal involvement will help clarify how much protection ADCs can offer. Dr Tarantino and Dr Mouabbi conclude that although current data are early, ADCs appear to be among the few systemic agents that may influence intracranial risk in breast cancer. They encourage clinicians to follow this area closely because additional evidence is expected from ongoing and planned trials.