Individualizing Neoadjuvant and Adjuvant ADC Strategies

This segment focuses on practical decision-making for integrating T-DXd into neoadjuvant and adjuvant treatment for early-stage HER2-positive breast cancer, emphasizing risk-adapted use and real-world implementation challenges. Clinicians highlighted that, based on DESTINY-Breast05, adjuvant T-DXd may be most appropriate for patients with very high-risk residual disease, particularly those with persistent nodal involvement who did not receive neoadjuvant T-DXd. For patients with lower-risk residual disease, T-DM1 remains a reasonable standard.

Safety considerations remain central, particularly the risk of ILD. Close radiographic monitoring is essential, with many clinicians favoring more frequent imaging than trial protocols to enable early detection in the curative-intent setting. Practical barriers such as scan logistics and insurance coverage may also affect implementation.

The discussion also explored treatment sequencing. For patients with very high-risk disease at presentation, neoadjuvant T-DXd may be preferred to maximize pCR rates and potentially allow less intensive postoperative therapy. If T-DXd is used preoperatively, many clinicians would transition to T-DM1 postoperatively and reserve T-DXd for future metastatic use if needed.

More broadly, the conversation reflects a shift toward both escalation for high-risk patients and de-escalation for selected lower-risk groups. Emerging biomarkers, including HER2 expression levels and novel scoring systems, may further refine patient selection by identifying those most likely to achieve pCR and benefit from tailored therapy. Overall, early-stage HER2-positive management is becoming increasingly personalized as ADC data mature.