Selective elimination of surgery for early invasive breast cancer: promise, challenges, and prospects

Kuerer et al. recently reported on the selective omission of breast surgery in patients achieving radiologic and pathologic complete response (pCR) following neoadjuvant systemic therapy (NST) in a multicentre phase II prospective study published in JAMA Oncology (1). While this study represents a potentially paradigm-shifting approach to breast cancer management, several critical limitations and considerations must be addressed before such a strategy can be translated into standard clinical practice.

The study employed image-guided vacuum-assisted biopsy (VAB) to determine pCR. However, the meta-analytical evidence cited has notable limitations, particularly the inclusion of diverse biopsy techniques such as fine needle aspiration (FNA), core needle biopsy (CNB), and VAB using different needle sizes, which compromises the reliability of its conclusions (2). When isolating data from VAB (7–10 gauge) alone, the pooled negative predictive value (NPV) approaches 80%, indicating that approximately one in five cases may be incorrectly classified as complete responders. Although no recurrences were observed in the false-negative cohort of Kuerer’s study, the small sample size and limited follow-up period hinder any definitive assessment of long-term oncologic safety, especially for triple positive breast cancer, which may recur many years after treatment. Moreover, diagnostic reproducibility may vary across clinical settings, particularly in community or lower-volume centres, highlighting the need for standardised imaging protocols and biopsy techniques.

Despite the study’s title, surgical procedures were not entirely eliminated. Patients who initially presented with node-positive disease still underwent targeted axillary dissection (TAD), even after achieving breast pCR. This reflects surgical de-escalation rather than full omission. Given that axillary pCR rates often exceed those of the breast, particularly in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC), there is a rationale for prioritising axillary surgery omission in selected patients. Emerging evidence supports the omission of axillary surgery in clinically node-negative patients with favourable tumour biology, with post-NST sentinel node positivity rates as low as ~2% (3).

Although VAB is less invasive than surgical excision, it carries its own procedural risks. Using a 9-gauge needle and sampling ≥12 cores can lead to complications such as haematoma, infection, persistent pain, and scarring. While findings from the Swedish vacuum-assisted excision (VAE) randomised clinical trial suggest that patient experience and healthcare costs are generally favourable (4), the procedure lacks the benefits of surgical excision, such as direct visualisation of the resection cavity, assessment of margins, and immediate reconstruction options. These limitations may negatively impact cosmesis and patient satisfaction, reinforcing the importance of thorough, informed shared decision-making.

Oncological safety is another concern. The potential for tumour cell dissemination or seeding during biopsy, particularly in cases with residual disease, warrants consideration. However, since patients typically undergo radiotherapy following the procedure, these risks are significantly mitigated. Both experimental and clinical evidence indicate that radiotherapy can reduce the risk of local recurrence resulting from biopsy-induced disruption (5,6). Moreover, systemic therapy and radiotherapy protocols help neutralize any potential impact of tumour cell dissemination.

Radiotherapy planning in the absence of surgical pathology can be complex but is feasible. Organized radiotherapy departments can utilise existing tumour markers and detailed pre-NST imaging to define treatment fields. Tumour bed locations are typically marked at initial diagnosis, and comprehensive imaging provides anatomical reference points for radiation planning. Future trials should emphasize the development of standardised imaging-based boost protocols and incorporate tumour subtype-specific radiosensitivity to ensure precise treatment delivery.

Although the study references favourable patient-reported outcomes, the instruments used were not specified and may be susceptible to recall and perception bias. Robust assessments using validated tools like BREAST-Q and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-BR23 are essential to accurately gauge the quality-of-life impact of surgical omission. Furthermore, longitudinal data are necessary to determine whether the observed psychological benefits are sustained or merely delay anxiety related to recurrence.

The study’s findings also raise questions regarding molecular residual disease detection. A notable discordance exists between this trial and prior research on liquid biopsy. Earlier studies reported circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) positivity rates of 65% and 43%, respectively, in post-NST blood samples for patients with early TNBC (7), whereas Kuerer et al. observed these markers in only ~15% of participants, with no overlap. This disparity may reflect variations in assay sensitivity, timing, or biomarker selection. Expanding molecular residual disease evaluations to include epigenomic or transcriptomic profiling and other liquid biopsy tools (8) could enhance predictive accuracy.

It is also important to recognise that this approach may only be applicable to a limited subset of patients. HER2-positive and TNBC cases, which are associated with pCR rates above 50%, represent a minority of breast cancer diagnoses. Conversely, oestrogen receptor (ER)-positive, HER2-negative tumours, which account for the majority of cases, typically exhibit pCR rates below 20%. This raises legitimate concerns about residual disease and the risk of delayed recurrence. Genomic risk stratification using tools like Oncotype DX and classification via intrinsic subtypes such as Prediction Analysis of Microarray 50 (PAM50) can help refine patient selection for surgical omission. In the I-SPY trial, hormone receptor (HR)⁺/HER2-negative early breast cancer showed a 17% pCR rate overall, rising to 31% among patients with high MammaPrint scores (9).

Beyond the neoadjuvant context, the concept of surgical omission may also extend to the upfront setting. In such cases, exceptional responders to systemic therapy might be considered for surgical de-escalation. However, this requires even more stringent selection criteria and monitoring protocols, given the absence of neoadjuvant response data. Reliance on tumour biology, imaging characteristics, and molecular markers becomes paramount. Elderly patients with early-stage, highly hormone-sensitive tumours who respond well to endocrine therapy and have significant comorbidities may represent viable candidates. Still, the current evidence supporting surgical omission in the upfront setting remains extremely limited and should only be explored within the framework of rigorously designed clinical trials with comprehensive safety oversight.

Conclusions and Future Directions

While the selective elimination of surgery is an appealing strategy, current evidence from Kuerer et al.’s study supports this only in rigorously selected patients within tightly controlled trial environments. The observed false-negative rate likely benefited from stringent inclusion criteria, advanced magnetic resonance imaging (MRI) interpretation, and extensive tissue sampling. Notably, a recent case series reported no recurrence in seven patients who declined surgery following an exceptional response to NST, with a median follow-up of 67 months (10).

Nevertheless, significant challenges remain—including biopsy accuracy, oncologic safety, radiotherapy planning, molecular surveillance, and generalisability. Upcoming prospective multicentre studies are expected to address these gaps. The OPTIMIST trial (11), for instance, aims to confirm the non-inferiority of 5-year disease-free survival in patients omitting surgery based on predicted pCR using MRI and VAB, compared to historical surgical cohorts. This trial also includes quality-of-life evaluations and seeks to mitigate concerns about undertreatment due to false-negative classifications and recurrence risks. Future studies should further assess the potential for radiation therapy omission in exceptional responders.

As these trials mature, they may herald a new era of risk-adapted, minimally invasive strategies for carefully selected patients. Ultimately, surgery in breast oncology could shift from the cornerstone of treatment to one component of a comprehensive, individualised systemic management algorithm. This paradigm aligns with the growing recognition that breast cancer is a multifaceted disease—an intricate ecosystem in which the primary tumour interacts with its microenvironment, the circulatory system, and distant organs (12).

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-191/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-191/coif). K.M. has received honoraria for offering academic and clinical advice to Merit Medical and Q Medical corporations. He owns shares in HCA Healthcare UK. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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