Axillary de-escalation after neoadjuvant systemic therapy in cN0-1 breast cancer patients

Background Recent advancements in breast cancer management have focused on de-escalating axillary surgery to minimize morbidity and improve quality of life, without compromising survival outcomes. Prior clinical trials have provided evidence supporting the use of less extensive axillary procedures in patients with favorable characteristics. However, research and evidence regarding optimal axillary lymph node surgical decisions after neoadjuvant systemic therapy (NAS) remain limited. Our study aimed to identify key factors in a real-world setting that predict the feasibility of omitting axillary surgery following NAS in clinically node negative (cN0) and clinically staged N1 (cN1) breast cancer. Methods We retrospectively analyzed 1068 clinical N0-1 breast cancer patients who received NAS followed by surgery. Univariable and multivariable logistic regression analyses were used to identify clinicopathological predictors for: (1) ypN0 after NAS in newly diagnosed cN0 patients, which could guide sentinel lymph node biopsy (SLNB) omission; and (2) ypN0 after NAS in newly diagnosed cN1 patients, which could guide axillary lymph node dissection (ALND) omission. Results In newly diagnosed cN0 patients (n = 302), 274 (90.7%) achieved ypN0. Achieving radiological partial response (rPR) after NAS (odds ratio (OR), 0.27; 95% CI, 0.11–0.65; P  = 0.003) was associated with a higher ypN0 rate, suggesting potential for SLNB omission. Conversely, higher clinical T stage (cT3-4) (OR, 3.06; 95% CI, 1.11–8.39; P  = 0.030) and estrogen receptor (ER) positivity (OR, 3.94; 95% CI, 1.24–12.54; P  = 0.020) were associated with a lower ypN0 rate, indicating a tendency towards retaining SLNB. In newly diagnosed cN1 patients (n = 766), the ypN0 rate was 50.3% (385/766). Human epidermal growth factor receptor 2 (HER2) positivity (OR, 0.34; 95% CI, 0.25–0.48; P  < 0.001), achieving rPR (OR, 0.38; 95% CI, 0.24–0.59; P  < 0.001), and achieving radiological complete response (rCR) (OR, 0.06; 95% CI, 0.02–0.14; P  < 0.001) were associated with a higher ypN0 rate, potentially allowing for selective ALND omission. However, tumors located in the central quadrant (OR, 2.99; 95% CI, 1.05–8.50; P  = 0.040), along with ER positivity (OR, 1.82; 95% CI, 1.16–2.84; P  = 0.009), progesterone receptor (PR) positivity (OR, 1.67; 95% CI, 1.08–2.56; P  = 0.020) and invasive breast carcinoma of special type (IBC-ST) (OR, 2.76; 95% CI, 1.05–7.22; P  = 0.039) were associated with a lower ypN0 rate, suggesting caution in omitting ALND. Conclusion For newly diagnosed cN0-1 breast cancer patients undergoing NAS, the post-NAS radiological assessment was a critical factor in guiding axillary surgical management decisions. Furthermore, in newly diagnosed cN1 patients, HER2 positivity was also associated with a higher ypN0 rate, which may inform the omission of ALND.