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HER2-low expression in breast oncology: treatment implications in the smart chemotherapy era
Federica Giugliano1,2, Giuseppe Curigliano1,2, Paolo Tarantino1,2,3,4
1Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS.
Abstract:
Human epidermal growth factor 2 (HER2)-low breast cancers, defined as tumors exhibiting a HER2 IHC score of 1+ or 2+ nonamplified, represent an emerging targetable entity in the clinicopathologic landscape of breast cancer. Traditionally considered as not sensitive to HER2-targeting agents, these tumors have shown to be susceptible to a new class of drugs, namely antibody-drug conjugates (ADCs). Indeed, the DESTINY-Breast04 phase 3 trial demonstrated the remarkable activity of trastuzumab deruxtecan for treating both hormone-receptor (HR)-positive and triple-negative metastatic breast cancers that show HER2-low expression, reshaping treatment algorithms for these diseases. Concomitantly, the TROPiCS-02 and the ASCENT phase 3 trials have established the role of the anti-Trop-2 ADC sacituzumab govitecan for HR-positive and triple-negative breast cancer, respectively. A careful evaluation of these trials, with their inclusion/exclusion criteria, efficacy and toxicity results, is required in order to understand how best to treat HER2-low metastatic breast cancer in the context of a rapidly evolving therapeutic landscape. The purpose of this narrative review is to recapitulate the available evidence on the use of ADCs in the treatment of HER2-low breast cancer, providing a perspective on their current role in clinical practice.
Insights
New antibody-drug conjugates (ADCs) show significant promise for treating HER2-low breast cancer, including hormone-receptor-positive and triple-negative subtypes. These advancements are reshaping treatment strategies for metastatic breast cancer patients.
Area of Science:
- Oncology
- Translational Research
- Clinical Therapeutics
Background:
- Human epidermal growth factor 2 (HER2)-low breast cancers (IHC 1+ or 2+ nonamplified) were traditionally unresponsive to HER2-targeted therapies.
- These tumors represent a significant subset of breast cancer with distinct therapeutic needs.
- Recent advancements have identified novel treatment strategies for this patient population.
Approach:
- This narrative review synthesizes evidence from key clinical trials, including DESTINY-Breast04, TROPiCS-02, and ASCENT.
- The review examines inclusion/exclusion criteria, efficacy, and toxicity data of antibody-drug conjugates (ADCs) in HER2-low breast cancer.
- It provides a clinical perspective on the evolving treatment landscape.
Key Points:
- Antibody-drug conjugates (ADCs) like trastuzumab deruxtecan and sacituzumab govitecan demonstrate significant efficacy in HER2-low metastatic breast cancer.
- Trastuzumab deruxtecan shows activity in both hormone-receptor-positive and triple-negative HER2-low breast cancers.
- Sacituzumab govitecan is established for hormone-receptor-positive and triple-negative breast cancer treatment.
Conclusions:
- ADCs represent a paradigm shift in treating HER2-low metastatic breast cancer, offering new therapeutic options.
- Careful evaluation of trial data is crucial for optimizing treatment selection in this rapidly evolving field.
- This review provides insights into the current role and future perspectives of ADCs for HER2-low breast cancer.
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