Adjuvant chemotherapy in stage I triple-negative breast cancer: A systematic review and meta-analysis of survival outcomes.

BACKGROUND

The benefit of adjuvant chemotherapy in patients with surgically-resected, stage-I TNBC remains controversial, especially when tumors are smaller than 10 mm in maximum diameter. We conducted a meta-analysis to evaluate the impact of adjuvant chemotherapy on survival outcomes in this setting, with prespecified subgroup analyses by pathological tumor size (pT1a/b/c).

METHODS

This study followed PRISMA guidelines and was registered in PROSPERO. Literature search from PubMed, EMBASE, Cochrane (2000-2025) and recent conference proceedings was reviewed for studies comparing overall survival (OS) and/or breast cancer-specific survival (BCSS) in stage I TNBC patients receiving adjuvant chemotherapy versus no chemotherapy. Hazard ratios (HR) were pooled using fixed- or random-effects models according to prespecified heterogeneity criteria (Q statistic, P < 0.10 and/or I2 > 25%). Small-study effects and robustness were evaluated with Egger's test and influence diagnostics.

RESULTS

Twenty-seven studies including 98,499 patients were analysed. Adjuvant chemotherapy resulted in significantly improved OS (HR 0.53, 95%CI 0.42-0.68; p < 0.001) and BCSS (HR 0.70, 95%CI 0.62-0.79; p < 0.001). In pT1a tumors, we found no benefit in terms of OS (HR 0.97, p = 0.91) or BCSS (HR 1.49, p = 0.12). In pT1b disease, chemotherapy use was associated with improved OS (HR 0.68, p < 0.0001), while no BCSS benefit was observed (HR 1.01, p = 0.94); this subgroup analysis should be interpreted cautiously. Finally, in pT1c tumors, adjuvant chemotherapy was associated with improved OS (HR 0.46, p < 0.0001) and BCSS (HR 0.68, p < 0.001).

CONCLUSIONS

In surgically-resected stage I TNBC, the association between adjuvant chemotherapy and better survival appears to vary according to tumor-size, with more consistent benefit in patients with tumors > 5 mm and no significant survival advantage observed in pT1a disease. These findings support a tailored, size-based approach, although the OS results should be interpreted cautiously given the observational nature of the evidence and the substantial heterogeneity of the pooled OS analysis.