Background
Metastatic breast cancer, also known as stage IV breast cancer, is characterized by the spread of malignant cells to distant sites at diagnosis. While systemic therapy remains the cornerstone of management, the role of local interventions such as breast surgery in this setting has been debated. Retrospective data have suggested possible survival benefits, but these findings are prone to selection bias and other methodological limitations. Given improvements in systemic therapy and longer survival times, clinicians have questioned whether removing the primary tumor could confer additional clinical advantages, especially in specific patient subgroups.
Study Design
This updated Cochrane systematic review evaluated randomized controlled trials (RCTs) that compared breast surgery plus systemic therapy to systemic therapy alone in women with de novo metastatic breast cancer. The search encompassed multiple databases including MEDLINE, Embase, CENTRAL, and trial registries, up to April 2023.
Inclusion criteria were:
– Adult women diagnosed with metastatic breast cancer at presentation.
– Randomized allocation to either breast surgery plus systemic therapy or systemic therapy alone.
– Primary outcomes: overall survival and quality of life.
– Secondary outcomes: progression-free survival (local and distant), breast cancer-specific survival, and local therapy toxicity.
A total of five RCTs were included, comprising 1368 women. Follow-up periods ranged from 3.5 to 10 years. Variations existed across trials in terms of randomization timing, inclusion criteria, and requirement for systemic therapy response prior to surgery.
Key Findings
Overall Survival: Across five studies, there was no statistically significant improvement in overall survival for women randomized to breast surgery plus systemic therapy compared with systemic therapy alone (HR 0.89, 95% CI 0.75–1.05; moderate-certainty evidence). This suggests that although surgery may reduce local tumor burden, it does not translate into longer life expectancy for most patients.
Subgroup Analyses: Exploratory data indicated possible variation by immunohistochemical subtype:
– Luminal tumors: modest improvement in survival (HR 0.82, 95% CI 0.69–0.96; moderate-certainty).
– HER2-positive or triple-negative disease: no survival benefit observed.
– Menopausal status, bone-only versus multiple metastases: little to no difference noted.
These analyses were exploratory, not definitive, and require cautious interpretation.
Quality of Life: Two studies assessed patient-reported outcomes:
– At 6 months: no improvement (MD 1.91, p=0.40, low-certainty).
– At 18 months: temporary benefit (MD 6.09, p=0.004, low-certainty).
– At 24 months: benefit was not sustained (MD 2.74, p=0.28).
Local Control: Breast surgery provided a substantial and statistically significant reduction in local disease progression (HR 0.43, 95% CI 0.32–0.58; high-certainty evidence).
Distant Progression-Free Survival: No improvement detected (HR 1.19, 95% CI 0.86–1.66; moderate-certainty evidence).
Toxicity: Only one study assessed toxicity, reporting no impact on 30-day mortality rates.
Expert Commentary
The absence of a survival benefit from breast surgery in de novo metastatic breast cancer aligns with contemporary guidelines that emphasize systemic therapy as the mainstay treatment. Local control benefits are clear, but whether these translate into meaningful improvements in quality of life is uncertain beyond the short term. The exploratory finding of benefit in luminal tumors suggests the potential value of precision medicine approaches, where patient selection based on tumor biology could guide surgical decisions.
Importantly, these RCTs reflect patient populations with variable systemic therapy responses and disease distributions. Surgical intervention may be considered in selected patients for symptom control, local complications prevention, or psychological benefit, although these indications need rigorous study.
Conclusion
Evidence from five RCTs indicates that breast surgery in women with de novo metastatic breast cancer reliably improves local disease control but does not improve overall survival. Subtype-specific benefits remain speculative. Quality of life improvement appears transient. Decisions regarding breast surgery should apply individualized assessment, weighing local control advantage against surgical risks, patient preferences, and systemic disease burden.
Funding and Clinical Trial Registration
This review is registered in ClinicalTrials.gov: NCT05285332.
Reference:
Tosello G, Riera R, Torloni MR, Neeman T, Cruz MR, Freitas IF, Christofaro D, de Paulo TRS, Oliveira CB, Mota BS. Breast surgery for metastatic breast cancer. Cochrane Database Syst Rev. 2025 Nov 20;11(11):CD011276. doi: 10.1002/14651858.CD011276.pub3 IF: 9.4 Q1 . PMID: 41263247 IF: 9.4 Q1 ; PMCID: PMC12631959 IF: 9.4 Q1 .