Risk-Adapted Optimization of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer
Cet article passe en revue les données supportant la désescalade des traitements néoadjuvants pour les cancers du sein HER2+ de stade précoce, examine l'arrivée du trastuzumab déruxtécan pour les formes à haut risque ainsi que les stratégies basées sur les biomarqueurs pour une désescalade thérapeutique plus poussée puis propose un cadre pour optimiser les traitements adaptés au risque, soulignant le potentiel de l'ADN tumoral circulant et de l'imagerie fonctionnelle pour personnaliser les traitements
Women with stage II to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer commonly receive neoadjuvant therapy. Recent trials have substantially expanded treatment options for these individuals. Randomized trial data indicate that carboplatin can be safely omitted from neoadjuvant therapy for most patients with stage II HER2-positive early-stage breast cancer, with comparable pathological complete response rates and reduced toxicity. Here, we review evidence supporting de-escalation in the neoadjuvant setting from docetaxel or paclitaxel, carboplatin, trastuzumab, pertuzumab to docetaxel or paclitaxel, trastuzumab, pertuzumab with weekly paclitaxel and examine biomarker-guided strategies for further de-escalation, including chemotherapy-free approaches. DESTINY-Breast11 and DESTINY-Breast05 have established the use of neoadjuvant and postneoadjuvant fam-trastuzumab deruxtecan-nxki, respectively, as new options for high-risk disease, with both indications recently granted approval from the U S Food and Drug Administration. We propose a framework for risk-adapted treatment optimization, highlighting the potential of circulating tumor DNA monitoring and functional imaging as response-adapted strategies and identifying them as priorities for future investigation. Together, these advances support a more precise, individualized approach to caring for patients with early-stage HER2-positive breast cancer.
Journal of Clinical Oncology , résumé, 2026