Dr. Rao addresses the significant challenge of CNS metastases in HER2-positive metastatic breast cancer, noting that most of her sickest patients or those she has lost in recent years succumbed to CNS progression. The availability of systemic therapies with CNS activity represents a major advancement beyond traditional radiation approaches.
She describes evolving screening practices, acknowledging no routine standard recommendation for CNS screening at metastatic diagnosis but increasingly screening more patients than in previous years. The decision involves weighing early detection benefits against psychological burden and treatment implications.
For patients presenting with brain metastases at diagnosis, T-DXd plus pertuzumab represents the clear choice given proven CNS efficacy data. The combination’s demonstrated improvement in brain metastasis-free survival from DESTINY-Breast09 supports this approach for patients with established CNS involvement.
Dr. Kruse explains her practice evolution regarding CNS screening, previously avoiding it when treatment options were limited or more toxic. However, increased comfort with T-DXd’s CNS activity and tolerability has changed this approach, as effective early intervention makes detection valuable rather than merely prognostic.
She emphasizes that initial brain metastases often represent “the tip of the iceberg,” making aggressive early CNS treatment beneficial for long-term control. For clinicians still weighing T-DXd versus THP decisions, CNS involvement provides strong rationale favoring the combination approach.
The panel discusses increasing recognition of subtle neurological symptoms that warrant CNS evaluation, including headaches, vision changes, and other neurological manifestations. They note particular concern about leptomeningeal disease in recurrent populations, given historical adjuvant therapies’ extracranial but not intracranial efficacy.
Early CNS screening is becoming more common among community providers, facilitated by improved MRI approval processes and greater awareness of treatment implications for CNS-positive patients.
