Melinda L. Telli, MD

Panelists discuss how the continued evolution of HER2-directed therapies, particularly the expanding role of trastuzumab deruxtecan (T-DXd) across different breast cancer settings, has transformed the treatment landscape, while emphasizing the importance of appropriate patient selection, optimal sequencing strategies, and the need for education around early adoption of promising therapies in community practice settings.

Panelists discuss how emerging data from trials such as DESTINY-Breast09, which is evaluating first-line trastuzumab deruxtecan (T-DXd) with or without pertuzumab, could potentially reshape the treatment paradigm for HER2+ metastatic breast cancer (mBC) by establishing new standards for initial therapy and optimal combination approaches.

Panelists discuss how sequential therapy selection for patients with HER2+ breast cancer with progressive brain metastases requires careful consideration of prior treatments, patterns of progression, symptom burden, and available clinical trials, while balancing the need for both systemic disease control and CNS -specific approaches.

Panelists discuss how the DESTINY-Breast12 trial evaluated trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer (mBC) with brain metastases, demonstrating encouraging intracranial responses and overall survival outcomes while maintaining a manageable safety profile consistent with previous T-DXd studies.

Panelists discuss how treatment selection for patients with HER2+ breast cancer with brain metastases requires careful consideration of factors such as metastatic burden, symptomatology, and prior therapies, typically incorporating both local approaches and systemic agents with CNS activity while accounting for individual patient characteristics such as performance status, comorbidities, and preferences in developing personalized treatment plans.

Panelists discuss how patients with HER2+ breast cancer frequently develop brain metastases, with recent pivotal trials such as HER2CLIMB and DESTINY-Breast03 demonstrating improved intracranial responses with newer agents such as tucatinib, and how trastuzumab deruxtecan leads to evolving standards of care (SOC) that now incorporate these targeted therapies alongside traditional local therapies.

Panelists discuss how trastuzumab deruxtecan’s (T-DXd's) key adverse events (AEs) include interstitial lung disease, neutropenia, and nausea/fatigue, emphasizing the importance of proactive monitoring, early intervention through coordinated multidisciplinary care, and comprehensive patient education with clear communication channels for reporting symptoms.

Panelists discuss how trastuzumab deruxtecan (T-DXd) demonstrated favorable patient-reported outcomes and quality of life measures in HER2-low hormone receptor-positive metastatic breast cancer patients in DESTINY-Breast06, suggesting it could be a well-tolerated therapeutic option that maintains patients' daily functioning while providing clinical benefit.

Panelists discuss how emerging data on HER2-ultralow breast cancer is informing treatment decisions, particularly regarding the potential role of trastuzumab deruxtecan, while acknowledging the need for careful patient selection and consideration of traditional treatment sequences.

Panelists discuss how DESTINY-Breast06 demonstrated meaningful clinical activity of trastuzumab deruxtecan in both HER2-low and ultralow metastatic breast cancer populations.

Panelists discuss how clinical trials like DESTINY-Breast04, TROPiCS-02, and TROPION-Breast01 have revolutionized treatment options for HER2-low advanced breast cancer by validating novel targeted therapies and antibody-drug conjugates.

Panelists discuss how evolving HER2 classification methods and recent trial data are reshaping treatment approaches for advanced breast cancer, particularly regarding the clinical significance of HER2-low and ultralow categories.

The panel looks to the future landscape for HER2+ breast cancer, highlighting emerging treatment practices and currently unmet needs.

Focusing on the selection of subsequent therapies for patients with HER2-low/HER2+ metastatic breast cancer, the panel discusses treatment sequencing considerations and practices.

Breast cancer specialists discuss adverse events associated with T-DXd, focusing on monitoring for interstitial lung disease (ILD) and the role of re-challenging patients with T-DXd after resolution of grade 1 ILD.

Aditya Bardia, MD, MPH, shares comprehensive insights on the DESTINY-Breast06 study evaluating T-DXd in HER2-low and HER2 ultra-low metastatic breast cancer, and the panel offers its initial impressions.

Ian Krop, MD, PhD, provides an overview of HER2-low and HER2 ultra-low breast cancer and discusses challenges encountered during diagnosis.

Experts on breast cancer discuss the potential impact of ongoing research in HER2+ breast cancer, highlighting how results from the DESTINY-Breast07 study may translate to DESTINY-Breast09.

Melinda Telli, MD, provides an overview of ongoing research in HER2+ metastatic breast cancer, highlighting the DESTINY-Breast09, PATINA, INAVO122, and HER2CLIMB-05 studies.

The panel provides comprehensive insights on approaching first-line treatment of patients with HER2+ metastatic breast cancer and the role of neratinib.

Breast cancer specialists outline their institution’s practices regarding the choice between subcutaneous fixed-dose pertuzumab – trastuzumab-hyaluronidase and intravenous pertuzumab and trastuzumab.

Kandace P. McGuire, MD, provides clinical insights on how patient monitoring practices inform discussions around surgical options, providing the potential for deescalating surgical management.

Ian Krop, MD, PhD, outlines his institution’s approach to utilizing neoadjuvant therapy in patients with HER2+ early breast cancer, and Melinda Telli, MD, discusses the role of surgery.

A panel of experts on breast cancer provide insights on challenges encountered during the diagnosis of HER2+ early breast cancer and discuss the role of immunohistochemistry and FISH testing.

Panelists wrap up their discussion on HER2+ breast cancer by summarizing the most exciting recent advances in the field and their hopes for the future of treatment.

Dr Kaklamani presents a profile of a patient with HER2+ breast cancer and liver metastases who had disease progression after first-line chemotherapy and a solitary new brain metastasis after second-line T-DM1.

Melinda L. Telli, MD, presents a profile of a patient with early stage breast cancer with residual nodal disease after neoadjuvant chemotherapy and surgery, whose tumor was initially HER2+ but became triple-negative after treatment.

Virginia G. Kaklamani, MD, DSc, presents a patient profile of early stage HER2+ breast cancer with residual nodal disease after neoadjuvant chemotherapy and surgery.

Experts share their go-to regimens in the third-line and higher setting of HER2+ metastatic breast cancer, and touch on the factors that support their decision-making.

Debu Tripathy, MD, discusses novel therapies being developed for later-line treatment of HER2+ mBC.