Comparison of targeted axillary dissection with sentinel node biopsy alone on nodal recurrence for patients who have node-positive breast cancer treated with neoadjuvant chemotherapy: a critical appraisal

The recent study by Boyle et al. published in the Annals of Surgical Oncology compared targeted axillary dissection (TAD) with sentinel lymph node biopsy (SLNB) alone in patients with node-positive breast cancer treated with neoadjuvant chemotherapy (NAC) (1). While the authors conclude that both methods offer excellent staging and regional control with low axillary nodal recurrence rates, we believe there are critical limitations not sufficiently addressed.

First, the short-term follow-up period of 28 months is inadequate to draw conclusions about the long-term safety and efficacy of SLNB alone. Axillary recurrence, as the primary endpoint, may underestimate the potential risks of omitting axillary lymph node dissection (ALND). Given the higher false-negative rate of SLNB compared to TAD, understaging remains a concern. Our recent pooled analysis (2) highlights the increased false-negative rates of SLNB in post-neoadjuvant systemic therapy settings. Clinical trials continue to explore the optimal axillary treatment in patients with positive axillary staging after NAC (3).

Additionally, the study’s reliance on axillary recurrence as the sole measure of regional control overlooks the implications of undetected nodal disease, which could affect adjuvant systemic therapy and radiation planning (3). The absence of overall survival (OS) data limits the ability to assess whether the observed outcomes reflect meaningful long-term benefits or risks. OS is a key clinical endpoint, directly reflecting the benefit of therapeutic interventions in breast cancer treatment (4).

The study’s small sample size of 44 patients who avoided ALND is another significant limitation. This cohort may not fully capture variability in outcomes or account for confounding factors, which severely limits the generalizability of the findings. A larger sample size would be essential to strengthen the conclusions and improve statistical power. The small number of observed axillary recurrences further compounds this limitation, making it impossible to draw definitive conclusions about differences between TAD and SLNB alone, regardless of the reported statistical significance.

Moreover, the analysis mainly focuses on univariate associations using the Chi-squared and Kruskal-Wallis tests. A multivariate analysis would help control for confounding variables, such as age, tumor size, and biological subtype, offering a clearer understanding of the independent effect of the surgical technique on outcomes. Additionally, the choice of statistical tests should be justified based on data distribution and variable characteristics. The authors did not specify whether they assessed the assumptions for the statistical tests, which is essential for validating the results.

Another critical limitation is the absence of routine axillary ultrasound in monitoring for recurrence. Monitoring through physical exams and mammograms alone is insufficient for detecting axillary recurrence, which could lead to significant underreporting of recurrence rates (5). This methodological flaw further undermines confidence in the study’s primary outcome measure and reported recurrence rates.

A fundamental issue not adequately addressed in the original study is the distinct purpose of SLNB versus TAD. SLNB is primarily a prognostic tool, while TAD serves both prognostic and therapeutic functions. When the clipped node that was initially positive is not specifically targeted and removed, as may occur with SLNB alone, there is no reliable way to confirm whether that specific disease site has achieved pathologic complete response (pCR). This is analogous to randomly sampling breast parenchyma rather than specifically evaluating the site of the original tumor to determine treatment response. The underperformance in clipped node retrieval with SLNB alone therefore has profound implications for the accurate assessment of treatment efficacy that extend beyond simple technical considerations (6).

The findings regarding clipped node retrieval further underscore the limitations of the SLNB-alone approach. However, the authors do not discuss the clinical significance of this underperformance (6). Clarifying how these impacts patient outcomes would enhance the clinical relevance of the study.

In conclusion, longer follow-up and incorporation of OS as a key endpoint are essential to establish the safety and oncologic adequacy of SLNB alone in this context. Until such data are available from adequately powered studies with appropriate monitoring and statistical analysis, significant caution is warranted in adopting SLNB alone as standard practice for patients with initially node-positive disease treated with NAC.

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-2025-152/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-152/coif). K.M. has received honoraria for offering academic and clinical advice to Merit Medical. The other authors have 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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References

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