Strategic Sequencing in HER2+ Breast Cancer: Optimizing Treatment in the Third Line and Beyond

EP: 1.Current Treatment Approaches in HER2+ Metastatic Breast Cancer

EP: 2.Optimizing Maintenance Therapy After First-Line Treatment in HER2+ Metastatic Breast Cancer

EP: 3.The Evolving Role of T-DXd in HER2+ Metastatic Breast Cancer

EP: 4.Strategies for Monitoring and Managing T-DXd-Related Adverse Effects

EP: 5.Patient Case Presentation: A 47-Year-Old Woman With HER2+ mBC and CNS Progression

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EP: 6.Strategic Sequencing in HER2+ Breast Cancer: Optimizing Treatment in the Third Line and Beyond

The panel discussed a patient who is currently at her third line of therapy for metastatic HER2-positive breast cancer with brain metastases. Given her disease status, the preferred next step is a regimen known to be effective in this setting, especially for patients with active central nervous system (CNS) involvement. A commonly used treatment with demonstrated intracranial activity is often recommended, while the exact sequencing of newer agents remains under discussion. Treatment decisions must carefully consider how CNS metastases influence the choice of therapy and whether options are available that balance efficacy and patient convenience.

In discussing prior treatments, it’s important to explore why the patient discontinued a certain therapy that was not stopped due to disease progression. Reasons such as intolerable adverse effects, logistical challenges of frequent infusions, or inadequate management of symptoms like nausea and fatigue need to be addressed before choosing subsequent therapies. Radiation history also plays a role, as concerns about radiation necrosis after stereotactic radiosurgery may impact decisions regarding continuation or reintroduction of targeted agents. Timing between radiation and systemic therapy is critical in minimizing risks and maximizing benefits.

Finally, while the selected treatment regimen is appropriate for the patient’s current condition, it is important to acknowledge practical challenges, such as the need for regular institutional visits for infusions. Although some therapies provide impressive disease control, they can impose burdens on patients due to administration requirements. Anticipating future lines of therapy is essential, as patients with CNS disease often require multiple sequential treatments. Tailoring therapy to individual patient needs and preferences, while closely monitoring CNS disease, remains a key aspect of modern metastatic breast cancer care.