Ruta Rao, MD

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.

Panelists discuss evolving frontline treatment strategies and future directions in HER2+ breast cancer, focusing on the latest advancements and emerging approaches in managing this subtype.

Panelists discuss a clinical scenario involving tucatinib-based regimens in the management of brain metastases in the second-line metastatic setting, exploring treatment options and clinical decision-making.

Panelists discuss intracranial efficacy data with tucatinib and T-DXd in the treatment of brain metastases, highlighting key findings and their implications for clinical practice.

Panelists discuss the strategic screening and management of brain metastases in HER2+ breast cancer, focusing on current approaches and emerging strategies to address this complication.

Panelists discuss how a third-line approach for a 54-year-old patient treated with a tucatinib-based regimen involves careful consideration of prior treatment responses, comorbidities, and the potential benefits of combining tucatinib with capecitabine and trastuzumab to improve outcomes in HER2+ metastatic breast cancer.

Panelists discuss how a third-line approach for a 54-year-old patient treated with a tucatinib-based regimen involves careful consideration of prior treatment responses, comorbidities, and the potential benefits of combining tucatinib with capecitabine and trastuzumab to improve outcomes in HER2+ metastatic breast cancer.

Panelists discuss how managing trastuzumab deruxtecan (T-DXd)–related toxicity and intolerance in later-line HER2+ breast cancer requires close monitoring, early detection of adverse effects like interstitial lung disease, and strategic adjustments to treatment regimens for improved patient safety and outcomes.

Panelists discuss how clinical data and treatment selection in later-line HER2+ metastatic breast cancer are informed by the latest therapeutic advancements, including targeted therapies like trastuzumab deruxtecan (T-DXd) and tucatinib, to optimize patient outcomes and manage progression.

A look at the evolving role of neurooncologists in the treatment of patients with HER2+ breast cancer and brain metastases and future perspectives in the management of this patient population.

Experts have a conversation of the use of trastuzumab deruxtecan therapy for patients with progressive brain metastases while weighing common toxicities and clinical trial data.

Sara Hurvitz, MD, presents the case of a 66-year-old woman with ER+ HER2+ invasive ductal carcinoma and brain metastases.

A look at exciting clinical trials enrolling patients with HER2+ breast cancer and leptomeningeal disease, a previously unheard-of opportunity.

A neuro-oncologist explains the prevalence of leptomeningeal metastases in HER2+ breast cancer and her preferred method of treatment.

Oncologists debate the use of neratinib for metastatic HER2+ breast cancer treatment in the context of the HER2CLIMB clinical trial data on tucatinib.

Dr Stefania Maraka presents the case of a 53-year-old woman with de novo metastatic mutated ER/PR+ HER2+ breast cancer and brain metastases.

Experts discuss their choice of systemic therapies after a patient with metastatic HER2+ breast cancer and brain metastases progresses on tucatinib therapy.

Ruta Rao, MD, discusses her rationale for treating metastatic HER2+ breast cancer with a tucatinib-containing regimen based on data from the HER2CLIMB trial.

Stefania Maraka, MD, explains the second- and third-line treatment options for metastatic HER2+ breast cancer and how she collaborates with breast oncologists.

Dr Sara Hurvitz provides an overview of HER2+ breast cancer, and Dr Ruta Rao details the frontline treatment options available for metastatic cases.

Ruta Rao, MD, presents the case of a 36-year-old woman with metastatic HER2+ breast cancer and brain metastases.