Abstract

Abstract Background Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomized controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question. Objectives To assess the effects of breast surgery on long term outcomes of women with metastatic breast cancer. Search methods We conducted searches using the MeSH terms ’breast neoplasms’, ’mastectomy’, and ’analysis, survival’ in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 08 December 2021. Selection criteria The inclusion criteria were randomized controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy. Data collection and analysis Two review authors independently conducted trial selection, data extraction, and ’Risk of bias’ assessment (using Cochrane’s ’Risk of bias’ tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies. Main results We included four trials enrolling women with metastatic breast cancer in the review. These studies included 961 participants, 477 in the surgery group, and 485 in the control group. The evidence suggests that surgery does not improve overall survival as the quality of the evidence has been assessed as very low (HR 0.92, 95% CI 0.72 to 1.18; 4 studies; 961 women). The evidence suggests that surgery does not improve overall survival subgroup analysis according to the number of metastasis sites (HR 1.08, 95% CI 0.74 to 1.58; 3 studies, 320 women); bone metastasis only (HR 0.86, 95% CI 0.67 to 1.11; 3 studies, 253 women). According to the tumor subtype surgery seems not improve the overall survival in triple-negative (HR 1.10, 95% CI 0.53 to 2.28; 3 studies, 132 women) and HER 2 positive profile (HR 0.83, 95% CI 0.63 to 1.11; 3 studies, 262 women). However, for patients with luminal tumors surgery can significantly or marginally increase the survival (HR 0.81, 95% CI 0.67 to 0.98; 3 studies, 547 women). Breast surgery may improve local progression-free survival (HR 0.48, 95% CI 0.27 to 0.84; 3 studies; 686 women; low-quality evidence), while it does not change distant progression-free survival (HR 1.03, 95% CI 0,77 to 1.36; 3 studies; very low-quality evidence). Two studies reported quality of life outcomes, however it was not possible to perform a meta-analysis due to different tools used by these trials. Authors’ conclusions Based on existing evidence from four randomized clinical trials, breast surgery does not to improve overall survival for women with metastatic breast cancer. However, in subgroup analysis, women with luminal tumors present increase in survival. The quality of evidence was very low and the decision to perform breast surgery on these women should be individualized and discussed by a multidisciplinary team considering the potential risks, benefits, and costs of each intervention. Citation Format: Giuliano Tosello, Rachel Riera, Diego Christofaro, Crystian Oliveira, Marcelo Cruz, Thais R. Paulo, Bruna S. Mota. Breast surgery for metastatic breast cancer: a Cochrane systematic review. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-16.

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