AIMS: The presence of ductal carcinoma in situ (DCIS) alongside invasive ductal carcinoma (IDC) of the breast is common in clinical practice and affects clinical outcomes and treatment strategies. This study aimed to compare the clinicopathological characteristics and prognosis of patients with IDC coexisting with DCIS versus pure IDC after neoadjuvant therapy (NAT) and to explore the risk factors for residual DCIS following NAT. MATERIAL AND METHODS: Patients with Stage II-III IDC who underwent NAT followed by radical surgery between January 2015 and December 2022 were included. Baseline data, clinical characteristics, preoperative treatment, surgical approach, pathological outcomes, and prognostic information were collected and analysed. RESULTS: A total of 852 patients were enrolled in this study, with 279 and 573 patients in the IDC + DCIS and IDC groups, respectively. Compared with patients in the IDC group, those in the IDC + DCIS group had a lower proportion of triple-negative molecular type (15.1% vs. 33.9%, P <
0.001), better histological grade (52.0% vs. 37.7%, P <
0.001), and higher residual rate of DCIS (71.3% vs. 38.7%, P <
0.001). The 5-year disease-free survival (DFS) (85.2% vs. 82.4%, P = 0.188) and overall survival (OS) (93.2% vs. 93.0%, P = 0.810) rates of patients in the IDC + DCIS group were similar to those in the IDC group. However, in the triple-negative breast cancer population, the DFS (88.6% vs. 75.8%, P = 0.032) of patients with IDC + DCIS was significantly better than that of patients with IDC. For patients with IDC + DCIS, age ≥40 years (odds ratio [OR] = 0.421
95% confidence interval [CI], 0.163-0.889, P = 0.035) and HR+/HER2-molecular subtype (OR=3.347
95% CI, 1.237-6.577, P = 0.047) were independent preoperative predictors for residual DCIS after NAT. CONCLUSION: The presence of DCIS in IDC demonstrated less tumour aggressiveness than pure IDC. However, a survival benefit was only observed in patients with triple-negative IDC combined with DCIS after NAT. Furthermore, patients with IDC + DCIS have a higher risk of residual DCIS after NAT, and age <
40 years and the luminal subtype are risk factors for residual DCIS after NAT in patients with IDC + DCIS.