Abstract Objectives: Over the last decade, axillary management strategies for patients with breast cancer have experienced several paradigm shifts toward surgical de-escalation, especially in exceptional responders who have achieved a complete response after neoadjuvant systemic therapy (NST). Current trends in axillary surgery for breast cancer patients who achieved clinical complete response (cCR) to neoadjuvant systemic therapy (NST) are unknown. Methods: In this retrospective cohort study, female patients diagnosed with breast cancer who achieved cCR after NST were selected from the Surveillance, Epidemiology, and End Results database (2010-2021). The proportions of patients undergoing each axillary treatment approach were summarized by year of diagnosis to assess the trend of axillary management strategy. The Cox proportional hazard models with the inverse probability of weighting (IPW) were used to evaluate the effects of axillary surgery on overall survival (OS) and disease-specific survival (DSS). A multivariate logistic regression model was used to explore factors associated with axillary pathological (p)CR. Results: In total, 15,111 patients were included. The nodal positivity rate after NST in cCR patients with initially clinical node-negative breast cancer was only 0.56%, while the nodal negativity rate after NST in cCR patients with initially clinical node-positive breast cancer was 49.57%. Between 2010 and 2021, axillary lymph node dissection (ALND) rates decreased from 55.27% to 29.07% while sentinel lymph node biopsy (SLNB) rates increased from 41.04% to 64.84%. From 2010 to 2021, the percentage of patients with initially node-negative disease receiving ALND after NST decreased from 32.92% to 13.03%, whereas those receiving SLNB increased from 66.24% to 80.82%. Patients who received ALND had worse OS than those who received SLNB (hazard ratio HR = 1.662, 95% confidence interval CI, 1.339-2.063, P .001). After applying the inverse probability weighting (IPW), patients in the ALND group still had a worse OS than those in the SLNB group (HR = 1.491, 95%CI, 1.164-1.911, P .001). Meanwhile, patients who received ALND were associated with worse DSS than those who received SLNB (HR = 1.909, 95%CI, 1.485-2.453, P .001). Despite the application of IPW, the DSS of patients in the ALND group remained inferior to that of the SLNB group (HR = 1.654, 95%CI, 1.243-2.202, P .001). The logistic regression analysis revealed that initial cN0 was a strong predictor of axillary pCR. Patients who were initially diagnosed with N1 (OR, 0.024; 95% CI, 0.022-0.027), N2 (OR, 0.036; 95% CI, 0.029-0.043), and N3 (OR, 0.028; 95% CI, 0.023-0.034) stages had a decreased odds of achieving axillary pCR. Conclusions: In summary, the results of this study indicated that ALND was administered to up to 13% of patients with originally node-negative breast cancer who achieved cCR following NST. Compared to SLNB, ALND may reduce the survival of patients who obtained nodal pCR, indicating potential overtreatment. In this subgroup of patients, we recommend carrying out SLNB first to determine the node status before the decision to undergo ALND. Citation Format: Y. Zheng, Y. Chen, E. Xia, O. Wang. Trends in axillary surgical strategies for breast cancer patients with clinical complete response after neoadjuvant systemic therapy: a population-based retrospective cohort study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-03-21.
Zheng et al. (Tue,) studied this question.