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Risk-Adapted Optimization of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer.

Created on 10 Sep 2026

Authors

Sam O Kleeman, Vered Stearns

Published in

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Pages JCO2601423. Sep 09, 2026. Epub Sep 09, 2026.

Abstract

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.

PMID:
42715513
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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