Omission of breast surgery in exceptional responders after neoadjuvant chemotherapy-what are future possibilities?-a narrative review.

Background and Objective: Triple negative and human epidermal growth factor receptor 2 (HER2)-positive (+) tumors exhibit excellent response to systemic therapy and are known as "exceptional responders". Pathological complete response (pCR) rates have been reported in up to 64% of triple negative breast cancer (TNBC) and 66% of HER2+ patients. The idea of surgical omission has been studied for many decades, but how it will fit into breast cancer practice is unclear. The goal of this review is to provide a comprehensive discussion of the relevant literature surrounding omission of surgery and potential surgical de-escalation for multifocal/multicentric (MF/MC) tumors after neoadjuvant chemotherapy (NAC). Methods: A literature search with relevant keywords was performed on the PubMed database and University of Rochester Edward Miner Library for studies ranging from 1989-2024. Types of studies included review articles, clinical trials and retrospective studies. A total of 49 studies were reviewed and summarized in this narrative review. Key Content and Findings: It is difficult to accurately predict pCR after NAC. Physical exam and imaging are not accurate and image-guided biopsies can have false negative rates (FNR) up to 49.3%; however, with careful patient selection FNR can be as low as 2.9%. Surgical omission trials are ongoing with promising preliminary results, but sample sizes are small, and while physician attitudes towards surgical omission are generally positive, the proportion of patients willing to omit surgery is low. Instead of omission of surgery altogether, an alternative potential for surgical de-escalation is avoidance of mastectomy. The literature on surgical de-escalation for TNBC, HER2+ MF/MC tumors is scarce as most of the surgical omission studies were performed on unifocal tumors. If MF/MC tumors have similar biology and morphology, pCR of the primary site could serve as an indicator of response at the other satellite sites, but more research needs to be done in this area. Conclusions: Surgical omission studies are ongoing with promising results. Patient attitudes and preferences of surgical omission should be considered as more clinical trials are planned. There is concern about the application of this concept broadly with the resources that are available. Large scale studies with longer follow-up is needed to confirm the safety of surgical de-escalation in this high-risk group of patients.