De-escalating breast surgery after neoadjuvant therapy: can surgery be omitted in exceptional responders?—A narrative review

Background and Objective: Neoadjuvant therapy (NAT) is utilized for most triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with pathologic complete response (pCR) rates approaching 65%. Despite high response rates, surgery remains standard practice following NAT. Increasing evidence suggests that a subset of patients with exceptional response to NAT may be candidates for surgery omission. The objective of this paper is to examine criteria for patient selection, diagnostic performance of post-treatment imaging and biopsy techniques, and to discuss key challenges, emerging strategies, and future directions of this de-escalation approach.

Methods: A literature search of published and ongoing trials investigating surgery omission after NAT was conducted, including single-center feasibility studies, multicenter phase 2 trials, international randomized studies, and meta-analyses. PubMed and Embase were searched for English-language studies during January 1, 2012–March 12, 2026. Key outcomes assessed include pCR prediction accuracy, false-negative rates of biopsy, negative predictive value (NPV) of imaging and biopsy protocols, recurrence-free and overall survival, and patient-reported outcomes.

Key Content and Findings: In the inaugural and to-date only prospective clinical trial of selective omission of surgery based on percutaneous biopsy after NST, there were no local-regional recurrences and 100% recurrence-free survival at median follow up of 5 years. This landmark study utilized strict eligibility criteria and protocol-mandated biopsy techniques. Other studies utilizing variable imaging and biopsy protocols have not consistently met the NPV threshold required to justify widespread surgery omission. Emerging data suggests that standardizing vacuum-assisted biopsy (VAB) parameters optimizes diagnostic accuracy. Ongoing trials are exploring axillary surgery omission and novel strategies such as combined neoadjuvant chemoradiation and patient selection based solely on imaging. Patient-reported outcomes show high satisfaction and minimal decisional regret among those who omitted surgery.

Conclusions: Surgery omission in exceptional responders represents a promising advancement in breast cancer treatment de-escalation. Standardization of tumor bed biopsy techniques and imaging protocols and planned or ongoing additional clinical trials are necessary before routine implementation into practice. Future integration of validated predictive biomarkers and individualized treatment algorithms may enable safe, surgery-free breast cancer management in appropriately selected patients after NAT.