Prediction of axillary response in 5,262 patients with node-positive breast cancer treated with neoadjuvant chemotherapy: Results from the prospective multicenter AXSANA/EUBREAST-03/AGO-B-053 study.

505 Background: Axillary lymph node dissection (ALND) for node-positive breast cancer (BC) converting to clinical node-negativity after neoadjuvant chemotherapy (NACT) is increasingly being replaced by less invasive procedures, such as sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD). Concerns remain regarding the use of de-escalated procedures in patients with high initial nodal burden. We aimed to determine factors associated with nodal response, with a focus on tumor biology and nodal burden, to enable less extensive surgery without compromising oncological outcomes. Methods: AXSANA is an ongoing study investigating oncological and patient-reported outcomes after different axillary procedures in cN+ BC treated with NACT. In the present analysis, the impact of nodal involvement and tumor biology on axillary response was analyzed. The entire dataset is continuously and systematically monitored for data quality assurance. Results: 7,071 patients from 288 sites in 26 countries were included between June 2020 and January 7 th , 2026. Of these, 5,262 had completed surgery at the time of analysis. 2,341 patients (44.5%) had HR+ HER2- disease, followed by HR+ HER2+ (1,244; 23.6%), triple-negative (1,053; 20.1%) and HR- HER2+ (618; 11.7%). 91.3% of patients had an invasive ductal carcinoma of no special type (NST). 1,158 (22.1%) had ≥ 4 suspicious nodes at time of diagnosis. The highest nodal pCR rate (ypN0) was observed in patients with HR- HER2+ disease (86.1%), followed by HR+ HER2+ (70.7%), triple-negative (68.5%), and HR+ HER2- (30.5%; p < 0.001). Nodal pCR rate was higher in patients with NST tumors (55.6%), compared to those with invasive lobular (35.2%) and mixed histology (43.8%; p < 0.001). Patients with higher Ki67 (p < 0.001), higher grading (p < 0.001), multicentric tumors (p = 0.001), and without lymphangitis carcinomatosa (p = 0.046) were more likely to achieve nodal pCR in the univariate analysis. In contrast, the number of suspicious nodes at the time of diagnosis was not associated with axillary response (ypN0: 54.4% in pts. with 1-3 suspicious nodes vs. 53.6% in ≥ 4 suspicious nodes; p = 0.670). In the multivariable analysis, receptor status, Ki67, and grading, but not the number of suspicious lymph nodes at the time of diagnosis, were significantly associated with axillary response to treatment. Conclusions: This large prospective analysis shows that tumor biology, rather than the extent of nodal involvement is associated with axillary response to NACT. This challenges current guidelines and the common approach of restricting surgical de-escalation to patients with a low axillary tumor burden at presentation, and suggests that the selection of candidates for a potential de-escalation should be based on tumor biology rather than the extent of axillary disease at diagnosis. Clinical trial information: NCT04373655 .