Explore whether the axillary outcomes differ among HER2 positive subgroups receiving standard dual-targeted therapy, aiming to identify subgroups exhibiting enhanced sensitivity to NAT among HER2-positive/node-positive breast cancer patients. HER2 positive female patients with biopsy-proven node-positive disease from April 2020 to May 2023 were included. All patients underwent standard Neoadjuvant HER2-targeted dual therapy and axillary lymph node dissection (ALND) at Breast Surgery Center of Sichuan Cancer Hospital. Univariate and multivariate analyses were used to identify factors associate with axillary pathological complete response (ApCR). Statistical analysis and graphing were performed using SPSS 24.0 and GraphPad Prism 9.0 software. This study enrolled 215 HER2 positive patients with a total ApCR rate of 76.7%, which included 49 HER2 2+/FISH + and 166 HER2 3 + cases with approximate ApCR rates of 63.3% and 80.7% (P = 0.011). Univariate and multivariate analysis indicated that HER2 3 + disease (OR = 2.43, 95% CI 1.21-4.88, P = 0.012), Ki-67 >= 20% disease (OR = 3.00, 95% CI 1.26-7.13, P = 0.013) and NAC regimen of TCb (OR = 2.71, 95% CI 1.39-5.38, P = 0.004) were more likely to achieve ApCR. Further subgroup analysis revealed that HER2 3 + patients receiving TCb regimen showed the highest ApCR rate of 88% compared to other subgroups. HER2 3 + breast cancer had a higher ApCR rate than HER2 2+/FISH + breast cancer during Neoadjuvant HER2-targeted dual therapy. HER2 positive patients could benefit from NAC regimen of TCb in axillary response.