Introduction: This study investigated the differences in efficacy between IHC(2+)/FISH-positive and IHC(3+) in HER2-positive breast cancer (BC) during neoadjuvant chemotherapy (NAC) combined with trastuzumab and pertuzumab. The research also aimed to provide insight into treatment strategies for clinical HER2(2+)/FISH-positive and HER2(3+) BC.Materials and methods: A retrospective analysis was performed on the clinical and pathological data of patients with confirmed diagnoses of invasive BC treated via combined NAC and dual-target therapy who underwent surgery at the Breast Surgery Center of Sichuan Cancer Hospital between June 2019 and June 2022. The cor -relation between the clinicopathological characteristics and pathological complete response (pCR) was analyzed via the & chi;2 test, while logistic regression was performed using the SAS 9.4 statistical analysis software.Results: This study examined 224 patients with an overall pCR rate of approximately 59.82%, which included 36 IHC(2+)/FISH-positive and 188 IHC(3+) cases with approximate pCR rates of 41.67% and 63.30%, respectively. Univariate and multifactorial analysis of the clinical and pathological data determined that age, menstrual status, family history, Ki67 expression, number of treatment cycles, and treatment regimen did not influence pCR. No statistical differences were evident between the univariate and multivariate models. However, the clinical stage, hormone receptor, and HER2 expression status significantly impacted pCR, with considerable consistent dif-ferences between the univariate and multifactor analyses.Conclusions: HER2 IHC(3+) BC displays a higher pCR rate than HER2 IHC(2+)/FISH-positive BC (p & LE; 0.05), with a positive correlation between the HER2 protein expression levels and the response to anti-HER2 therapy.