Introduction: The Evolving Landscape of Axillary Management
For decades, the surgical management of the axilla in breast cancer has trended toward de-escalation. From the routine use of radical axillary lymph node dissection (ALND) to the adoption of sentinel lymph node biopsy (SLNB), the goal has been to reduce morbidity—specifically lymphedema and functional impairment—without compromising oncological safety. However, the management of patients who receive neoadjuvant chemotherapy (NAC) remains a complex frontier. While patients who achieve a complete pathological response in the nodes (ypN0) can safely avoid ALND, the management of low-volume residual disease, specifically micrometastases (ypN1mi), has remained a subject of intense debate. The OPBC-07/microNAC study provides critical, real-world evidence to guide this clinical decision-making.
Highlights of the OPBC-07/microNAC Study
- In a global cohort of 1,585 patients with residual micrometastases (ypN1mi) after neoadjuvant chemotherapy, the overall 3-year axillary recurrence rate was remarkably low at 2.0%.
- No significant difference in axillary recurrence was observed between patients who underwent completion ALND and those who did not.
- Triple-negative breast cancer (TNBC) was identified as a significant risk factor, with omission of ALND leading to higher recurrence rates in this specific subgroup (8.7% vs 2.4%).
- Nodal radiotherapy (RT) emerged as a critical protective factor; its omission was independently associated with an increased risk of recurrence.
Background: The Challenge of Residual Nodal Disease
Neoadjuvant chemotherapy is increasingly utilized for patients with clinically node-positive breast cancer to downstage the disease and assess chemo-sensitivity. When a patient initially presenting with biopsy-proven nodal involvement (cN+) is found to have only micrometastases (nodes >0.2 mm but ≤2.0 mm) after NAC, surgeons face a dilemma. Does this residual disease represent a resistant clone that necessitates full clearance, or can it be managed effectively with regional radiotherapy and systemic treatment? Until recently, data specifically addressing the ypN1mi population were scarce, leading to significant variations in international practice patterns.
Study Design and Patient Population
OPBC-07/microNAC was an international, retrospective cohort study involving 84 cancer centers across 30 countries. The study analyzed female patients (aged ≥18 years) with cT1-4, N0-3 breast cancer who received NAC followed by surgery between 2013 and 2023. Eligible patients were those found to have residual micrometastases on SLNB, targeted axillary dissection (TAD), or the MARI procedure.
The primary endpoint was the 5-year rate of any axillary recurrence (isolated or combined). For this analysis, 3-year rates were reported alongside exploratory 5-year estimates. The cohort was divided into two groups: those who underwent completion ALND (n=804) and those in whom ALND was omitted (n=781).
Key Findings: Safety and Subgroup Disparities
Overall Recurrence Rates
The study found that the 3-year rate of axillary recurrence for the entire cohort was only 2.0% (95% CI 1.3-2.9). When comparing the two surgical strategies, there was no statistically significant difference in recurrence between the ALND group and the ALND-omission group. This suggests that for a broad population of patients with ypN1mi disease, the additional surgical morbidity of ALND may not confer a survival or recurrence benefit.
The Impact of Tumor Biology
A critical finding of the study was the divergence in outcomes based on tumor biology. Patients with hormone receptor-positive/HER2-negative or HER2-positive disease fared well regardless of the extent of axillary surgery. However, in the triple-negative breast cancer (TNBC) subgroup, omitting ALND was associated with a significantly higher risk of axillary recurrence (8.7% in the omission group vs. 2.4% in the ALND group, p=0.018). This highlights that TNBC remains a biologically aggressive subtype where even low-volume residual disease may require more intensive regional control.
Multivariable Analysis and Predictive Factors
Multivariable analysis confirmed that the primary drivers of recurrence were not the extent of surgery itself, but rather tumor biology and the use of adjuvant therapy. Specifically:
- Triple-negative breast cancer was associated with a hazard ratio (HR) of 3.83 for recurrence.
- Omission of nodal radiotherapy was associated with a HR of 2.62.
- Omission of ALND was not independently associated with increased risk (HR 0.86), provided other treatments were optimized.
Expert Commentary: Contextualizing the Results
The OPBC-07/microNAC results align with a broader shift toward biological rather than purely anatomical staging. The low overall recurrence rate suggests that modern systemic therapies and targeted radiotherapy are highly effective at controlling microscopic residual disease in the axilla.
However, the TNBC data serve as a cautionary note. In TNBC, the presence of residual disease after NAC is a known marker of poor prognosis and chemo-resistance. The study suggests that for these high-risk patients, ALND might still play a role in ensuring regional control, or perhaps more intensive radiotherapy and systemic follow-up are required. Furthermore, the high rate of nodal radiotherapy in this study (nearly 80%) suggests that RT acts as a crucial safety net when ALND is omitted. Clinicians should be wary of omitting both ALND and nodal RT in the ypN1mi setting.
Clinical Implications and Limitations
These findings suggest that for most patients with ypN1mi disease after NAC, completion ALND can be safely omitted, particularly in those with luminal or HER2-positive subtypes who receive adjuvant nodal radiotherapy. This approach significantly reduces the risk of lymphedema and improves the quality of life for breast cancer survivors.
Despite its strengths, the study is limited by its retrospective nature and the median follow-up of 3.1 years. While axillary recurrences typically occur early, longer-term data (10-year outcomes) would be beneficial to confirm these findings. Additionally, because the study relied on institutional databases, there may have been inherent selection biases regarding which patients were offered ALND omission.
Summary and Conclusion
The OPBC-07/microNAC study provides a robust international benchmark for the management of residual nodal micrometastases after neoadjuvant chemotherapy. The data support the omission of ALND for the majority of these patients, provided that nodal radiotherapy is incorporated into the treatment plan. However, the significantly higher recurrence risk in triple-negative breast cancer underscores the need for a personalized approach where tumor biology dictates the intensity of surgical intervention. As we move forward, the integration of genomic profiling and better response-prediction tools will likely further refine which patients can safely skip the scalpel in the axilla.
Funding and Clinical Trial Information
This study was funded by the US National Institutes of Health and the National Cancer Institute. It is registered with ClinicalTrials.gov under the identifier NCT06529302.
References
1. Montagna G, Alvarado M, Myers S, et al. Oncological outcomes with and without axillary lymph node dissection in patients with residual micrometastases after neoadjuvant chemotherapy (OPBC-07/microNAC): an international, retrospective cohort study. Lancet Oncol. 2026;27(1):57-67. doi:10.1016/S1470-2045(25)00598-4.
