Heather McArthur, MD, MPH

Panelists highlighted the impressive central nervous system activity of trastuzumab deruxtecan demonstrated in the DX12 trial, underscoring the need for multidisciplinary collaboration to optimize treatment of brain metastases and reduce reliance on whole-brain radiation, while acknowledging ongoing challenges in sequencing and patient selection amid evolving therapies.

Panelists agreed that beyond third-line therapy for HER2-positive metastatic breast cancer, treatment becomes highly individualized—often described as the “wild West”—with options including various monoclonal antibodies, tyrosine kinase inhibitors, chemotherapy, and emerging agents; decisions are largely based on prior toxicities, patient preferences, and disease biology, with clinical trials playing a crucial role in offering promising new therapies that may outperform standard care.

Panelists highlighted that the HER2CLIMB study showed adding tucatinib to trastuzumab and capecitabine provides a meaningful progression-free survival benefit in HER2-positive metastatic breast cancer with brain metastases, balancing improved intracranial control against manageable toxicities like diarrhea and hand-foot syndrome, and underscored the importance of patient education and dose management to maintain adherence and quality of life.

Panelists emphasized that for a patient with metastatic HER2-positive breast cancer and active brain metastases, selecting a treatment with proven intracranial activity is critical, while carefully considering prior therapy tolerability, radiation history, and the balance between treatment efficacy and patient convenience to optimize both disease control and quality of life.

Panelists discussed a complex case of a 47-year-old woman with metastatic HER2-positive breast cancer, emphasizing the importance of continuous systemic therapy despite treatment interruptions, the critical role of multidisciplinary care for central nervous system involvement, and the need to balance efficacy with quality of life as patients navigate prolonged disease courses and evolving treatment strategies.

Panelists discussed the persistent risk of interstitial lung disease with trastuzumab deruxtecan, emphasizing the need for early detection through routine imaging, rapid intervention to prevent severe toxicity, and cautious retreatment in select cases where interstitial lung disease was mild and well managed.

Panelists discussed how DESTINY-Breast03 firmly established trastuzumab deruxtecan (T-DXd) as the second-line standard in HER2-positive metastatic breast cancer, while early DESTINY-Breast09 data suggest that T-DXd combined with pertuzumab may challenge the CLEOPATRA regimen in the frontline setting, though questions remain about global applicability.

Panelists discussed how maintenance therapy in HER2-positive metastatic breast cancer is evolving beyond traditional dual antibody approaches, with emerging strategies incorporating targeted agents like tucatinib and endocrine therapy to personalize care and potentially delay central nervous system progression.

Panelists discussed how evolving strategies in HER2-positive metastatic breast cancer are shifting toward more personalized maintenance approaches, including the integration of CDK4/6 inhibitors and endocrine therapy, with growing interest in chemotherapy-free options for select patients.

The panel closes their discussion by musing on the future of HER2 mBC treatments.

A discussion on the prevalence and treatment difficulties of leptomeningeal metastases in HER2+ mBC.

The panel discusses the systemic therapy options for patients with HER2+ mBC with brain metastases before moving to whole brain radiation therapy.

Andrew Brenner, MD, presents the case of a 62-year-old patient with stage II HER2+ mBC presenting with both pulmonary and brain metastases.

Joyce O’Shaughnessy, MD, starts a conversation on managing the adverse events of tucatinib therapy in patients with HER2+ mBC with brain metastases.

The panel reviews the treatment approaches for HER2+ mBC with active brain metastases and the factors to consider during treatment decision-making.

Virginia Kaklamani, MD, presents the case of a 60-year-old patient with stage III HER2+ mBC with brain metastases.

Heather McArthur, MD, describes what treatment options she would consider in the third-line setting for HER2+ mBC.

Andrew Brenner, MD, explains when physicians should screen patients with HER2+ breast cancer for brain metastases.

Joyce O’Shaughnessy, MD, starts a discussion on maintenance therapy with trastuzumab deruxtecan in patient with HER2+ mBC.

Heather McArthur, MD, presents the case of a 69-year-old woman with stage II HER2+ mBC for discussion.

Dr. McArthur discusses the latest results of immunotherapy trials in the treatment of triple-negative breast cancer.

Brain metastasis remains a relatively common and particularly devastating complication of breast cancer and has proven a particularly challenging area for therapeutic innovation.