Rapid relapse in triple-negative breast cancer: clinical patterns, platinum resistance, and implications for clonal evolution.

Background: Triple-negative breast cancer (TNBC) is characterized by high heterogeneity and poor prognosis. A particularly aggressive subset, termed 'rapid relapse' TNBC (rrTNBC), is defined by distant metastasis or death within 24 months of diagnosis. Understanding the unique recurrence patterns and prognostic determinants of rrTNBC is crucial for deciphering tumor evolution and optimizing therapeutic strategies. This study aims to delineate the clinicopathological features, recurrence patterns, and prognostic outcomes of rrTNBC compared to slow relapse TNBC (srTNBC). Methods: We retrospectively analyzed 638 postoperative patients with recurrent or metastatic TNBC treated at Tianjin Medical University Cancer Institute & Hospital. Patients were categorized into rrTNBC (relapse ≤24 months, n = 478) and srTNBC (relapse >24 months, n = 160). Clinicopathological variables, recurrence sites, and survival outcomes, including disease-free survival (DFS), progression-free interval (PFI) after first salvage therapy, post-recurrence survival (PRS), and overall survival (OS), were compared between the two groups. Results: Compared to srTNBC, rrTNBC was associated with higher TNM stage, T stage, N stage, and a lower proportion of stromal tumor-infiltrating lymphocyte expression (all p < 0.001). Regarding recurrence patterns, rrTNBC patients were more likely to present with visceral (74.90% vs. 22.50%, p < 0.001) and brain metastases (10.88% vs. 0.62%, p < 0.001) as the first event, whereas srTNBC patients had a higher incidence of first relapse in the chest wall or regional lymph nodes (90.00% vs. 62.13%, p < 0.001). Consequently, rrTNBC was characterized by a significantly higher rate of direct distant metastasis at first recurrence (93.10% vs. 28.12%, p < 0.001). Prognostically, rrTNBC patients had markedly worse outcomes across all metrics compared to srTNBC patients, including median disease-free survival (13.4 vs. 26.6 months), median PFI after first-line salvage therapy (2.27 vs. 8.43 months), median PRS (12.1 vs. 23.5 months), and median overall survival (26.5 vs. 52.0 months) (all p < 0.001). In the platinum-based first-line salvage therapy subgroup (n = 369), rrTNBC patients (n = 267) consistently demonstrated significantly shorter DFS, PFI, PRS, and OS compared to srTNBC patients (n = 102) (all p < 0.001). Conclusion: rrTNBC represents a distinct, highly aggressive phenotype with a predilection for visceral and brain metastasis and a dismal response to conventional platinum-based salvage therapy. These findings are consistent with the aggressive clonal evolution within rrTNBC and highlight an urgent need for novel therapeutic strategies to be prospectively evaluated in this high-risk population.