Abstract Introduction: The prognostic significance of achieving axillary pathologic complete response (AxpCR) following neoadjuvant chemotherapy (NAT) in clinically node-positive (cN+) breast cancer (BC) is well established. However, consensus regarding the optimal strategy for axillary management—particularly in patients with HER2-positive BC—remains lacking. This study aims to evaluate the predictive value of the maximum standardized uptake value of axillary lymph nodes (N-SUVmax) obtained from baseline 18F-FDG PET/CT scans, in combination with the absolute monocyte count (AMC), for AxpCR following NAT in patients with cN+ HER2-positive BC. Methods: A retrospective analysis was conducted on HER2-positive cN+ BC patients treated with NAT. All patients received the same chemotherapy regimen, including dual HER2 blockade. ROC curves were used to determine cut-off values for N-SUVmax and AMC. Associations with AxpCR were analyzed using logistic regression models. Results: Among 285 patients diagnosed with HER2-positive BC, 215 presented with cN+ disease at baseline. Of these, 155 patients (72.1%) achieved AxpCR following NAT. All patients underwent axillary lymph node dissection (ALND) according to current guidelines, regardless of imaging or biomarker results. Notably, a large proportion showed no residual nodal disease at pathology, confirming AxpCR despite initial cN+ status.Patients with an N-SUVmax ≥ 3.5 had a 4.9-fold higher likelihood of achieving AxpCR (p = 0.039; odds ratio OR = 4.938 95% CI: 1.081-1.904). In contrast, patients with an AMC 340/mm3 had a 90.4% lower probability of achieving AxpCR (p 0.001; OR = 0.096 95% CI: 0.028-0.324). Notably, the interaction between N-SUVmax and AMC was significant: higher AMC levels diminished the predictive value of N-SUVmax for AxpCR (p = 0.002; OR = 0.999 95% CI: 0.997-1.000). Based on N-SUVmax and AMC values, patients were stratified into three groups. Group 1: High N-SUVmax - Low AMC; Group 2: High N-SUVmax - High AMC or Low N-SUVmax - Low AMC; Group 3: Low N-SUVmax - High AMC. Compared to Group 1, both Group 2 (p 0.001; OR = 0.047 95% CI: 0.009-0.237) and Group 3 (p 0.001; OR = 0.017 95% CI: 0.002-0.137) showed significantly reduced probabilities of achieving AxpCR. Conclusions: Assessing axillary response to NAT in HER2-positive BC provides a critical opportunity to tailor surgical management. The combination of baseline N-SUVmax and AMC improves prediction of AxpCR and may support more individualized axillary treatment strategies, ultimately contributing to better patient outcomes. Citation Format: L. Raimondi, M. Cuzzocrea, C. Oliva, N. Peradze, Y. Harder, D. Schmauss, R. Graffeo Galbiati, L. Rossi. Guiding the Axilla: Combining SUVmax and Monocytes to Predict Response to Neoadjuvant Therapy in HER2 positive Breast Cancer 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 PS3-11-19.
Raimondi et al. (Tue,) studied this question.