Heather McArthur, MD, MPH

In 167 patients with HR+/HER2− breast cancer after neoadjuvant chemotherapy, lymphovascular invasion, number of positive sentinel nodes, and >50% positive sentinel nodes were the strongest predictors of high axillary burden; a nomogram was developed to guide axillary management decisions.

Panelists discuss how the expanding volume of clinical data—both positive and negative—is increasing treatment complexity while reinforcing the need for individualized, patient-centered decision-making.

Panelists discuss how toxicity monitoring and quality-of-life considerations must be adapted as potent therapies move into earlier-line and curative-intent settings.

Panelists discuss how identifying high-risk subgroups enables more precise selection of maintenance therapies that maximize progression-free survival while accounting for biomarker differences.

Panelists discuss how emerging neoadjuvant and adjuvant data in HER2-positive breast cancer are challenging traditional standards and supporting earlier use of highly effective agents.

Panelists discuss how results from antibody-drug conjugate trials, including those that fail primary endpoints, provide critical insights for refining sequencing strategies in hormone receptor–positive disease.

Panelists discuss how post-CDK4/6 endocrine strategies increasingly rely on molecular profiling to guide therapy selection and optimize benefit in resistant disease.

Panelists discuss how data from recent ESR1-mutant disease trials are influencing interpretation of survival end points, regulatory expectations, and real-world adoption of oral SERDs.

Panelists discuss how rapidly evolving guidelines are reshaping treatment pathways by preserving endocrine therapy as a backbone while introducing earlier use of combination regimens and ADCs.

Panelists discuss how sequencing targeted therapies after CDK4/6 inhibitors differs for patients with actionable mutations versus those without, incorporating evidence for rechallenge and combination strategies.

Panelists discuss how integrating both tissue and liquid genomic testing at diagnosis and progression improves detection of tumor heterogeneity and informs personalized treatment decisions in metastatic breast cancer.

Leading experts in the breast cancer field highlight the use of CDK4/6 inhibitors, antibody-drug conjugates, and other treatment modalities.

Leading experts in the breast cancer field highlight the use of CDK4/6 inhibitors, antibody-drug conjugates, and other treatment modalities.

In a discussion at IBC East, Heather McArthur, MD, highlighted how immunotherapy is being utilized for patients with early-stage breast cancer.

Heather McArthur, MD, spoke about the use of CDK4/6 inhibitors in the adjuvant setting for patients with HR+/HER2– breast cancer.

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.