Triple-negative breast cancer (TNBC) is notably associated with higher mortality compared to other breast cancer subtypes [21]. Several cohort studies have shown that nearly 50% of TNBC patients develop distant metastasis, typically within two years of diagnosis [14–17]. While studies on breast cancer recurrence often focus on late recurrences (more than five years post-diagnosis), which are common in estrogen receptor-positive and HER2-negative cases [22, 23, 24], there is a paucity of research on early recurrence factors specific to TNBC. This may be due to the relatively lower number of TNBC patients and the tendency for recurrence or metastasis within three years post-diagnosis [25, 26]. This study aims to fill this gap by identifying potential clinical predictive markers for rapid postoperative recurrence in TNBC, leveraging data from a large cohort of breast cancer patients at our center.
Our findings from univariate and multivariate analyses indicate that higher T and N stages significantly elevate the risk of rapid relapse in TNBC patients after routine postoperative adjuvant chemotherapy.This finding is consistent with previous studies [15, 27, 28, 29, 30].Specifically, patients with T2 and T3/T4 tumors have 2.557 and 3.7 times higher risk of rapid relapse compared to those with T1 tumors (T2 staging, OR = 2.557, 95% CI: 1.766–3.703; T3/T4 staging, OR = 3.7, 95% CI: 1.355–10.454). Similarly, the risk increases substantially with higher N stages: 3.056 times for N1, 6.917 times for N2, and 24.597 times for N3 compared to N0 (N1 staging, OR = 3.056, 95% CI: 2.021–4.619; N2 staging, OR = 6.917, 95% CI: 3.920-12.206; N3 staging, OR = 24.597, 95% CI: 11.875–50.948). These results suggest that larger tumors and more extensive lymph node involvement are strongly associated with a higher likelihood of early recurrence. We propose that the increased tumor burden in these cases likely facilitates the dissemination of tumor cells, particularly in the context of suboptimal systemic treatment outcomes.Other clinical features, such as pathological patterns, tumor grade, lymphovascular invasion, and Ki67 expression levels, have been associated with prognosis in triple-negative breast cancer (TNBC) [31, 32, 33, 34, 35]. However, our study found no significant correlation between these factors and rapid relapse after adjusting for T and N stages. This suggests that tumor size and nodal involvement may play a more pivotal role in determining the risk of early recurrence in TNBC. Furthermore, our findings necessitate further validation through larger, multicenter studies.
Demographic factors have also been explored in relation to TNBC outcomes. Professor Daniel G. Stover's analysis highlighted associations between rapid relapse and socioeconomic factors like insurance status, income, and younger age[36]. Although our study could not assess these factors due to data limitations, we observed that being aged 50 or older at diagnosis was protective against rapid recurrence, reducing the risk to 0.413 times that of patients younger than 50 (OR = 0.413, 95% CI: 0.289–0.590). These findings are consistent with previous reports[36, 37, 38]. We propose possible explanations for this observation: Younger TNBC patients may exhibit more aggressive disease due to factors like increased genomic instability and a higher prevalence of BRCA1/2 mutations [39, 40, 41, 42].
The tumor microenvironment (TME) plays a critical role in cancer progression. We examined markers such as stromal tumor-infiltrating lymphocytes (sTIL), P53, CK5/6, and EGFR. High sTIL expression, which often includes CD4 + and CD8 + T cells, was significantly protective against rapid recurrence, reducing risk by 0.204 and 0.020 times for intermediate and high expression, respectively (intermediate sTIL: OR = 0.204, 95% CI: 0.139–0.300; high sTIL: OR = 0.020, 95% CI: 0.011–0.035). This aligns with studies indicating that high sTIL levels correlate with improved survival [43, 44, 45, 46, 47, 48]. While P53, CK5/6, and EGFR are often associated with poorer outcomes [49, 50], our study did not find significant correlations with rapid relapse, suggesting a need for further research.
Antibody-drug conjugates (ADCs) exhibit a unique cytotoxic mechanism, effectively targeting not only HER2-overexpressing tumor cells but also impacting HER2-low expressing tumor cells through the bystander effect. Consequently, HER2-low expression has garnered attention with the introduction of therapies such as trastuzumab deruxtecan (T-DXd/DS-8201) [51, 52, 53]. Interestingly, our analysis identified HER2 1 + status as a protective factor against rapid recurrence, indicating a complex relationship between HER2 expression and outcomes in triple-negative breast cancer (TNBC) that warrants further investigation. Additionally, our study did not find significant associations between surgical approach, chemotherapy regimen, or radiotherapy and rapid relapse, despite existing evidence that these treatments can reduce recurrence and mortality in breast cancer [19, 54]. This underscores the necessity for personalized treatment strategies based on individual risk factors.