Discordance Between Breast and Nodal Pathologic Response in Triple‐Negative Breast Cancer: Methodological Considerations and Contemporary Implications

The recent systematic review by Cristófalo et al. evaluating breast and nodal pathologic complete response (pCR) following neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) provides an important synthesis addressing post-neoadjuvant surgical decision-making [1]. The reported observation that nodal pCR rates may exceed breast pCR rates across analyzed cohorts is clinically relevant and may influence ongoing discussions regarding axillary surgical de-escalation. However, several methodological aspects warrant further consideration. Breast pCR definitions differed among included studies, with some cohorts defining response as ypT0 while others used ypT0/is, whereas nodal response was consistently defined as ypN0. This lack of endpoint uniformity may unintentionally exaggerate the apparent discordance between breast and nodal responses and limit biologically meaningful comparisons when translating findings into surgical practice [1]. Furthermore, baseline axillary staging was heterogeneous, including both clinically suspected and biopsy-proven node-positive disease, while surgical assessment ranged from sentinel lymph node biopsy to axillary lymph node dissection. Such variability introduces verification bias and may affect reported nodal clearance rates, an issue previously emphasized in large meta-analytic evaluations of axillary response following neoadjuvant therapy [2]. Importantly, most cohorts included in the review reflect treatment eras preceding the routine incorporation of immune checkpoint inhibitors. Contemporary neoadjuvant regimens incorporating pembrolizumab substantially improve pCR outcomes in TNBC and may alter concordance between breast and nodal response patterns, thereby limiting extrapolation of historical pooled estimates to modern clinical practice [3]. Prospective validation or carefully designed retrospective analyses restricted to biopsy-confirmed node-positive TNBC treated with current systemic therapies are needed to determine whether breast pCR can reliably predict nodal sterilization and safely support axillary de-escalation strategies. The authors are to be commended for addressing a timely and clinically significant topic that continues to shape surgical management paradigms in TNBC. No artificial intelligence–generated content was used to create scientific data, interpretations, or conclusions in this manuscript. Artificial intelligence–based language assistance (ChatGPT, OpenAI, GPT-5.2) was used solely to improve language clarity and editorial organization under the full supervision and responsibility of the authors. All intellectual content, critical interpretation, and final manuscript approval were performed entirely by the authors. Artificial intelligence tools were not involved in study design and are not listed as authors. The author declares no conflicts of interest. The author has nothing to report. Heterogenous definitions of pathological complete response and variability in axillary staging may overstate breast-nodal response discordance in triple-negative breast cancer. Contemporary neoadjuvant immunotherapy further limits extrapolation of historiacal data to current axillary de-escalation decison-making.