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Antibody-Drug Conjugates in Breast Cancer: Spotlight on HER2
Rachel Occhiogrosso Abelman1, Arielle Medford, Laura Spring
1From the Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Abstract:
Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies linked to a cytotoxic payload, enabling targeted delivery of more potent chemotherapy. In the past decade, there has been rapid development of ADCs aimed at different types of breast cancer. The success of the monoclonal antibody trastuzumab has led to the evolution of several ADCs targeting HER2-positive breast cancer. Trastuzumab-emtansine, the first approved ADC targeting HER2-positive breast cancer, has become standard of care for patients with high-risk early-stage HER2-positive breast cancer who have residual disease after neoadjuvant chemotherapy. More recently, the observation of the bystander effect, in which ADCs target both antigen-positive cells and adjacent antigen-negative cells, has led to the reclassification of "HER2-low" breast cancer and the development of trastuzumab-deruxtecan to target this population. This article reviews the history of HER2-directed ADCs in breast cancer as well as ongoing ADCs in development.
Insights
Antibody-drug conjugates (ADCs) advance targeted breast cancer chemotherapy. Trastuzumab-based ADCs now treat HER2-positive and HER2-low breast cancer, with new agents in development.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in targeted cancer therapy, particularly for breast cancer.
- The development of ADCs leverages monoclonal antibodies to deliver potent cytotoxic payloads directly to cancer cells, enhancing treatment efficacy and minimizing systemic toxicity.
- The past decade has witnessed substantial progress in ADC development, with a focus on various breast cancer subtypes.
Approach:
- Reviewing the historical development of HER2-directed ADCs in breast cancer treatment.
- Highlighting the evolution from trastuzumab to newer agents like trastuzumab-emtansine and trastuzumab-deruxtecan.
- Discussing the impact of the bystander effect on ADC efficacy and the emergence of HER2-low breast cancer as a targetable population.
Key Points:
- Trastuzumab-emtansine is a standard of care for high-risk, HER2-positive early-stage breast cancer with residual disease post-neoadjuvant chemotherapy.
- The bystander effect, where ADCs affect both antigen-positive and antigen-negative cells, has broadened therapeutic strategies.
- Trastuzumab-deruxtecan targets the newly defined HER2-low breast cancer population, expanding treatment options.
Conclusions:
- HER2-directed ADCs have transformed the treatment landscape for HER2-positive breast cancer.
- Ongoing research and development are continuously expanding the utility of ADCs to encompass a wider spectrum of breast cancer, including HER2-low disease.
- The future of breast cancer therapy is increasingly influenced by the innovative application of antibody-drug conjugate technology.
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