Treatment Sequencing in HER2-Positive Early Breast Cancer

Dr. Jason Mouabbi discusses how the broader FDA neoadjuvant indication for HER2-positive early breast cancer may be interpreted in clinical practice relative to the more narrowly defined high-risk population enrolled in DESTINY-Breast11. He emphasizes the importance of individualized treatment decisions for patients who may not have met the trial eligibility criteria but could potentially benefit from an intensive neoadjuvant approach. The conversation then turns to treatment sequencing, with Dr. Mouabbi noting the flexibility reflected in current NCCN guidance regarding the positioning of THP and T-DXd. Dr. Ruta Rao explains that she generally follows the sequence evaluated in DESTINY-Breast11, administering four cycles of T-DXd followed by THP. She highlights the importance of minimizing interstitial lung disease (ILD) risk in the curative setting and notes the relatively low ILD rates observed in DESTINY-Breast11. Both physicians favor following the trial-tested sequence while acknowledging that future evidence could further inform the optimal sequencing of T-DXd and THP in HER2-positive early breast cancer.