ObjectiveTo investigate the influencing factors of total pathological complete response (tpCR) in newly treated human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients after neoadjuvant targeted chemotherapy, so as to provide more reference for the formulation of surgical plan and prognosis assessment. MethodsNinety-five newly treated HER2-positive breast cancer patients after neoadjuvant targeted chemotherapy were retrospectively chosen in the period from January 2021 to January 2023 in our hospital and all patients were divided into tpCR group (51 cases) and non-tpCR group (44 cases) according to whether tpCR was achieved after neoadjuvant targeted chemotherapy or not. Univariate and multivariate methods were used to evaluate the independent influencing factors of tpCR after neoadjuvant targeted chemotherapy in newly treated HER2-positive breast cancer patients. The prediction model based on the above independent influencing factors was constructed and the potential predictive efficacy of this model for tpCR after neoadjuvant targeted chemotherapy was evaluated. ResultsAmong 95 patients, 51 patients achieved tpCR after neoadjuvant targeted chemotherapy and 44 patients did not achieve tpCR. The results of the multivariate logistic regression model analysis showed that the patients with HER2 3+(OR=6.102, P=0.014), HER2+/hormone receptor– (HER2+/hormone receptor+ OR=0.129, P=0.006), and trastuzumab+pantomizumab treatment (OR=6.582, P=0.014) had higher tpCR rate, estrogen receptor 3+ (OR=0.122, P=0.0.033), progesterone receptor 3+ (OR=0.179, P=0.020), Ki-67 index of 15%–30% (OR=0.088, P=0.030) and 31%–60% (OR=0.066, P=0.017) had lower tpCR rate. The predicted area under the curve of this model was 0.881 [95%CI (0.815, 0.947)]. ConclusionsThe achievement of tpCR after new adjuvant treatment in newly diagnosed HER2 positive breast cancer patients is related to the expression level of HER2 in immunohistochemistry, molecular typing and new adjuvant targeted treatment scheme. At the same time, the prediction model based on these influencing factors can predict the effect of tpCR after new adjuvant treatment in patients to a certain extent.