Evolving Treatment Landscape for HER2+ Breast Cancer
A medical oncologist offers clinical insights on the evolving treatment landscape for patients with HER2+ 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.
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