[Association between molecular typing and prognosis with recurrence pattern in triple-negative breast cancer...

Objective: To analyze the association between molecular typing and prognosis with recurrence pattern in triple-negative breast cancer (TNBC) patients based on long-term follow-up of a multi-omics cohort. Methods: A retrospective analysis was performed on the clinical data and transcriptomic data of patients diagnosed with TNBC at Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 1, 2007, to December 31, 2014. The survival status of patients was documented, and the follow-up continued until the patients' death or August 31, 2025. According to the"Fudan subtype", the patients were categorized into the basal-like immune suppressed (BLIS), immunomodulatory (IM), luminal androgen receptor (LAR), and mesenchymal-like (MES). Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was employed to evaluate the differences in overall survival (OS), disease-free survival (DFS) and recurrence-free interval (RFI) among TNBC patients with different molecular subtypes. Multivariate Cox proportional hazards regression analysis was used to assess the association between"Fudan subtype"and OS, DFS and RFI. Differential expression analysis and subsequent gene set enrichment were conducted. Competing-risk models were used to calculate the cumulative incidence of lung metastasis after accounting for competing events, and the differences were assessed using the Fine-Gray test. Results: After excluding 9 patients lost to follow-up, a total of 351 patients with TNBC were included in the analysis. The mean age at baseline was 53.46±11.36 years, and the median follow-up duration was 102.09 months. During follow-up, 72 patients died and 84 experienced recurrence or metastasis. Among them, 134 patients were classified as the BLIS subtype, with 27 deaths (20.15%); 86 patients were classified as the IM subtype, with 11 deaths (12.79%); 81 patients were classified as the LAR subtype, with 22 deaths (27.16%); and 50 patients were classified as the MES subtype, with 12 deaths (24.00%). The 10-year RFI rates for the BLIS, IM, LAR, and MES subtypes were 80.12% (95%CI: 73.41%-87.44%), 92.35% (95%CI: 86.64%-98.43%), 81.92% (95%CI: 73.39%-91.44%), and 72.95% (95%CI: 61.37%-86.71%), respectively. Kaplan-Meier survival curves showed that the differences of RFI among the four molecular subtypes of patients were statistically significant (P=0.040). Multivariate analysis showed that LAR subtype (LAR vs IM, HR=2.41, P=0.042) was the independent risk factor for DFS, and BLIS subtype (BLIS vs IM, HR=4.17, P=0.011), LAR subtype (LAR vs IM, HR=3.49, P=0.040) and MES subtype (MES vs IM, HR=3.98, P=0.019) were independent risk factors for RFI. The BLIS subtype is more likely to develop recurrence or metastasis in the early postoperative period, particularly lung metastasis. Differential gene expression analysis showed that BLIS subtype-specific genes, including those involved in proliferation and cell cycle activity, were predominantly upregulated in tumors with early recurrence or metastasis. Competing-risk analysis demonstrated that BLIS patients had a higher cumulative incidence of lung metastasis both overall and within the first 5 years after surgery compared with non-BLIS patients (both P<0.05). Conclusion: The"Fudan subtype"was significantly associated with RFI in early-stage TNBC patients. In addition, recurrence and metastasis were more likely to be observed in the early postoperative period in the BLIS subtype, particularly early lung metastasis.