Purpose Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them. Methods Patients with PD during NST for stage I–III breast cancer diagnosed between 1 January 2008 and 31 July 2021 in Fudan University Shanghai Cancer Center were enrolled. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different ST strategies. Results Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.012) and not receiving direct surgery (p = 0.013) were independently associated with distant disease-free survival on multivariate analysis. Conclusions Predictors of distant failure in patients with PD include triple-negative breast cancer and not receiving direct surgery. We suggest that direct surgery should be considered first for operable patients. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.