Impact of Local Treatment of the Primary Tumor on Overall Survival in De Novo Metastatic Breast Cancer: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: The prognostic impact of local treatment (LT) of the primary tumor in patients with de novo metastatic breast cancer (dnMBC) remains unclear. We conducted a systematic review and meta-analysis to evaluate whether surgery and/or radiotherapy of the primary tumor improves overall survival (OS).

MATERIALS AND

METHODS

Electronic databases (PubMed, Embase, Cochrane) were searched up to March 2025 for studies comparing LT (surgery and/or radiotherapy) plus systemic therapy versus systemic therapy alone. Hazard ratios (HRs) for OS were pooled using a random-effects model. Subgroup analyses were performed by study design, treatment modality, biological subtype, and metastatic site. Heterogeneity was quantified using I², and meta-regression was used to explore potential moderators.

RESULTS

Twenty studies, including randomized controlled trials (RCTs) and retrospective studies, were included. In pooled analyses, LT was associated with improved OS compared to systemic therapy alone. [HR=0.62; 95% confidence interval (CI)=0.52-0.75; p<0.0001; I²=97.3%]. In RCTs, the difference was not significant (HR=0.91; 95% CI=0.67-1.25; p=0.57). Surgery of the primary tumor was associated with improved OS (pooled HR=0.62; 95% CI=0.52-0.75). In the radiotherapy-only subgroup, based on a very limited number of heterogeneous retrospective studies, no survival benefit was observed (pooled HR=1.51; 95% CI=0.87-2.63). Given the very limited number of studies and the substantial heterogeneity (I²=91.5%), these findings need to be interpreted with caution. Subgroup analyses showed a non-significant trend in hormone receptor-positive disease (HR=0.78; 95% CI=0.58-1.04) and no benefit in HER2-positive (HR=0.90; 95% CI=0.61-1.33) or liver-limited disease (HR=1.17; 95% CI=0.77-1.78). No covariates were significantly associated with OS in meta-regression.

CONCLUSION

Although pooled analyses suggest an association between local treatment and improved OS, this effect appears largely driven by retrospective data and is not confirmed in randomized trials.