Exploring the association between post-operative complications, disease-recurrence & mortality in primary operable breast cancer—systematic review & meta-analysis

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Background: Post-operative complications (POCs) affect 36.1% of breast cancer patients. POCs are associated with inferior oncological outcomes in gastro-intestinal, lung, and head and neck cancers. Evidence is less clear in breast cancer. The James Lind Alliance demonstrated the importance of exploring risk factors for disease-recurrence to both patients and clinicians. We reviewed the evidence and performed a meta-analysis to better understand the association between POCs, disease-recurrence and mortality in primary breast cancer. Methods: A PubMed search was conducted on 1st February 2024. Journal titles and abstracts were screened for suitability. Bibliographies of suitable studies were hand-searched for additional eligible studies. Original articles focusing on oncological outcomes after the development of POCs in primary breast cancer were included. Articles analysing risk factors for development of POCs or those assessing in situ or metastatic disease were excluded. Studies were evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random effects model and presented using Forest plots. Results: Sixteen original studies were included in our review. Two large population studies demonstrate inferior survival in elderly patients who develop major surgical or medical complications, however, neither study accounts for recurrence or cancer-specific survival. Evidence for other comorbidities is lacking. Mastectomy demonstrates increased POC risk and is associated with inferior survival compared to conservation surgery [overall: hazard ratio (HR) 1.32, 95% confidence interval (CI): 1.15–1.51; cancer-specific: HR 1.31, 95% CI: 1.04–1.65]. There is however a paucity of evidence exploring impact of POCs following oncoplastic and/or reconstructive surgery. Meta-analysis demonstrated a significant effect of POCs in increasing the risk of recurrence (HR 1.35, 95% CI: 1.17–1.56, P<0.001), though a high degree of heterogeneity was noted (I2=86%). Variability in ‘wound complication’ definition and associated incidence, as well as the primary outcome reported (locoregional; systemic; any-site recurrence) was noted. Meta-analysis demonstrated a significant impact of POCs on the risk of all-cause mortality (HR 1.27, 95% CI: 1.17–1.39, P<0.001), with no heterogeneity observed (I2=0%). Conclusions: Increased age and mastectomy increase the risk of POC with associated inferior survival. The impact on disease-recurrence remains uncertain. Prospective studies with well-defined criteria are required, alongside studies exploring cellular level changes in primary breast cancer to better understand the underlying mechanism.

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