T-DXd in Breast Cancer: Neoadjuvant vs. Adjuvant Use – Expert Insights
The evolving landscape of HER2-positive breast cancer treatment is prompting oncologists to reconsider the optimal timing of antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (Enhertu). Recent discussions, including a debate at the Miami Breast Cancer Conference, suggest that utilizing trastuzumab deruxtecan in the adjuvant setting – following initial surgery – may offer advantages over neoadjuvant use, where it’s administered before surgery. This shift in thinking centers on the potential to spare some patients the intensive treatment in the neoadjuvant phase, reserving the ADC for when it might be most impactful after surgery.
Trastuzumab deruxtecan, co-developed by AstraZeneca and Daiichi Sankyo, has demonstrated significant efficacy in treating HER2-positive breast cancer, even in cases resistant to other HER2-targeted therapies. As Healio reported in October 2025, the drug is being viewed as a potential new standard for high-risk HER2-positive breast cancer. The core of the debate lies in identifying which patients will benefit most from early exposure to this potent therapy.
Balancing Efficacy and Potential Spares
Dr. Paolo Tarantino, an advanced fellow at Dana-Farber Cancer Institute, articulated the rationale behind this evolving approach. “I do feel that makes sense because there are patients that can be spared [antibody-drug conjugates] in the neoadjuvant setting [and] only get them in the adjuvant setting instead,” he explained to Healio. This strategy acknowledges the significant side effect profile associated with ADCs and aims to minimize unnecessary exposure for patients who may achieve adequate disease control with other therapies initially.
The decision isn’t straightforward. Neoadjuvant treatment allows clinicians to assess the drug’s impact on tumor shrinkage, providing valuable information about its effectiveness in an individual patient. But, this benefit must be weighed against the potential for overtreatment and the cumulative toxicities of aggressive regimens. The adjuvant setting, even as lacking this immediate feedback, offers the opportunity to consolidate remission and address any residual disease after surgery.
Understanding HER2-Positive Breast Cancer and Targeted Therapies
HER2-positive breast cancer is characterized by an overabundance of the human epidermal growth factor receptor 2 (HER2) protein on the surface of cancer cells. This excess HER2 drives aggressive tumor growth. Targeted therapies, like trastuzumab and trastuzumab deruxtecan, specifically target this protein, disrupting cancer cell signaling and promoting cell death. The National Cancer Institute provides a comprehensive overview of targeted therapy for breast cancer, explaining how these drugs differ from traditional chemotherapy.
Trastuzumab deruxtecan represents a newer generation of HER2-targeted therapies. It’s an ADC, meaning it combines an antibody that recognizes HER2 with a potent chemotherapy drug. The antibody delivers the chemotherapy directly to the cancer cells, minimizing exposure to healthy tissues. However, this targeted delivery isn’t perfect and side effects can still occur.
The Miami Breast Cancer Conference Discussion
The debate at the Miami Breast Cancer Conference, where Dr. Tarantino participated, highlighted the complexities of this treatment decision. The conference, held March 5-8, 2025, brought together leading experts to discuss the latest advancements in breast cancer care. Healio provided coverage of the conference, noting the significant focus on HER2 and TROP2 therapies. The discussion underscored the demand for personalized treatment strategies, tailored to the individual characteristics of each patient’s cancer and their overall health status.
The presented data, as cited in the conference proceedings (Rugo HS, et al.), explored various pathways with HER2 and TROP2 therapies, from early to advanced stages of the disease. This research is crucial for refining treatment algorithms and optimizing outcomes for patients with HER2-positive breast cancer.
Disclosures and Conflicts of Interest
It’s important to note that Dr. Tarantino has disclosed financial relationships with several pharmaceutical companies, including AstraZeneca, Daiichi Sankyo, and others involved in the development and marketing of breast cancer therapies. These disclosures, as reported by Healio, are standard practice in medical conferences and publications, ensuring transparency and acknowledging potential biases. These relationships do not invalidate the clinical discussion, but This proves important for readers to be aware of them.
What’s Next: Refining Adjuvant Strategies
The ongoing research and clinical discussions surrounding trastuzumab deruxtecan are driving a refinement of adjuvant treatment strategies for HER2-positive breast cancer. Future studies will likely focus on identifying biomarkers that can predict which patients are most likely to benefit from neoadjuvant versus adjuvant therapy. This will involve analyzing tumor characteristics, genetic profiles, and patient-specific factors to personalize treatment decisions. Further investigation into managing the side effects of ADCs will also be critical to maximizing their benefit while minimizing harm. The goal is to deliver the right treatment, to the right patient, at the right time, optimizing outcomes and improving quality of life for individuals facing this challenging diagnosis.