Surgery-first versus neoadjuvant chemotherapy in stage I (cT1c) triple-negative breast cancer: A critical reappraisal

The incidence of Stage I breast cancer is rising due to the implementation of widespread screening programs. Current ESMO guidelines recommend neoadjuvant chemotherapy (NACT) for Stage I (cT1c) triple-negative breast cancer (TNBC), a strategy largely extrapolated from trials enrolling Stage II-III patients. This review critically reappraises the NACT paradigm specifically for the cT1c subgroup.

We analysed emerging real-world data, including large-scale SEER studies and recent meta-analyses, comparing survival outcomes of NACT versus adjuvant chemotherapy (ACT) in Stage I TNBC. Additionally, we evaluated the differential efficacy of platinum agents and capecitabine in the neoadjuvant versus adjuvant settings.

Retrospective analyses suggest that for Stage I TNBC, a surgery-first approach followed by ACT is associated with superior breast cancer-specific survival and overall survival compared to NACT. The survival benefit of NACT assumed in higher stages does not consistently translate to Stage I. Furthermore, while the addition of neoadjuvant carboplatin increases pathological complete response (pCR) rates, it yields inconsistent OS benefits. In contrast, adjuvant capecitabine demonstrates a robust long-term survival benefit.

We propose a stage-specific therapeutic algorithm for cT1c N0M0 TNBC favouring a surgery-first strategy followed by ACT. This approach optimizes survival outcomes by including adjuvant capecitabine within an anthracycline/taxane backbone while avoiding the potential pitfalls of neoadjuvant undertreatment in early-stage disease.