Evolving Treatment Landscape for HER2+ Breast Cancer

EP: 1.The Overall Breast Cancer Landscape

EP: 2.Recent Updates for Biomarker Testing in Breast Cancer

EP: 3.The Role of Ki-67 and ctDNA as Prognostic or Predictive Markers in Breast Cancer

EP: 4.CDK4/6 & PARP Inhibitors for Early-Stage Breast Cancer

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EP: 5.Evolving Treatment Landscape for HER2+ Breast Cancer

EP: 6.Key Updates in Metastatic HER2+ Breast Cancer

EP: 7.Treatment Landscape for Triple-Negative Breast Cancer

EP: 8.Emerging Therapies and Ongoing Trials in Breast Cancer

EP: 9.Clinical Pearls for the Treatment of Breast Cancer

EP: 10.Personalized Treatment Sequencing Is a New Way of Thinking in Breast Cancer

This is a synopsis of an OncView series featuring Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute.

Sara M. Tolaney, MD, MPH, Chief of Breast Oncology at Dana-Farber Cancer Institute, discussed the emergence of HER2-low breast cancer as an important new subgroup, falling between traditional HER2-negative and HER2-positive categories. HER2-low tumors show low-level (1+ or 2+) HER2 staining without amplification.

The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) showed significant improvements in progression-free and overall survival compared to chemotherapy in HER2-low metastatic breast cancer in the DESTINY-Breast04 trial. Benefit was demonstrated in both estrogen receptor (ER)-positive and triple negative subgroups, with ~50% response rates irrespective of ER status. This challenges the paradigm of tailoring therapy purely based on ER/HER2 phenotypes, showing benefit when the drug target HER2 is present even at low levels.

Given therapeutic implications, determining HER2-low status is now critical. However, reproducibly distinguishing HER2-low from HER2-negative cancers is challenging. In particular, pathologists struggle to differentiate HER2 0 versus 1+ cases, where HER2-negative tumors may show up to 10% staining. This subset, dubbed “HER2-ultralow”, is being evaluated in the DESTINY-Breast06 trial of T-DXd for metastatic disease. If positive, routinely gauging ultra-low HER2 expression could further evolve practice.

In summary, the recognition of HER2-low breast cancer – exhibiting low HER2 positivity between negative and positive thresholds – has opened the door to targeting these previously untapped patients with novel HER2-directed therapies like the antibody-drug conjugate T-DXd. While assays distinguishing low HER2 expression remain imperfect, this area is primed to progress with additional clinical data and pathological standardization to optimize patient selection for emerging targeted options.

*Video synopsis is AI-generated and reviewed by Cancer Network editorial staff.