Effect of local surgery on outcomes of stage IV breast cancer

Abstract

Metastatic breast cancer (MBC), including de novo stage IV, is regarded as being incurable and the mainstay of clinical management is systemic therapy. Traditionally, locoregional surgery is performed only for local control, such as to prevent ulceration and bleeding. In recent years, however, both retrospective and prospective studies have demonstrated the prognostic efficacy of primary surgery for de novo stage IV patients. Therefore, we conducted a meta-analysis to evaluate whether surgical therapy contributes to overall survival (OS) extension. We searched for clinical trials published in electronic databases (PubMed, Embase, and the Cochrane databases) and performed a meta-analysis of the data collected. There were five prospective randomized controlled phase III trials (RCTs). The results of three have been reported. According to our meta-analysis of these RCTs, primary surgery for de novo stage IV breast cancer patients significantly improves OS. However, the Tata trial showed that systemic therapy does not achieve a sufficient effect. Another trial, conducted in Turkey, had statistical shortcomings and patient randomization was not adequately performed The ABCSG (Austrian Breast and Colorectal Cancer Study Group) trial had too few subjects. Meta-analysis of 12 retrospective studies showed that patients with stage IV breast cancer receiving surgery as the initial treatment experienced longer OS (HR: 0.65, P<0.00001). Based on our meta-analysis of three reported RCTs, surgery as the primary treatment does not significantly impact the outcomes of de novo stage IV breast cancer patients. However, these trials had limitations. We await the results of the remaining two ongoing RCTs (ECOG 2108 and JCOG 1017). These trials are anticipated to resolve current controversies and provide many eagerly awaited answers.

Surgical Management of Metastatic Breast Cancer: A Mini Review

“…One meta-analysis of 19 retrospective studies revealed the pooled hazard ratio (HR) of local surgery vs. systemic therapy alone to be 0.65 with a 95% confidence interval (95% CI) of 0.60–0.71 (p < 0.01), indicating that overall survival was significantly improved by surgical resection of the primary lesion ( 4 ). This finding was supported by another meta-analysis of 12 retrospective studies (odds ratio, 0.65; 95% CI, 0.59–0.72) ( 5 ). A large meta-analysis of 34 retrospective studies and 3 prospective randomized studies found surgical resection to significantly reduce mortality (HR, 0.64; 95% CI, 0.60–0.68) ( 6 ).…”

Enzymatically Transformable Polymersome‐Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer

“…[ 13a,34 ] Several clinical trials have been initiated to test the effect of surgical removal on metastatic breast cancer. [ 35 ] The proposed nanotherapeutic strategy may be effective in managing surgery‐associated inflammation stress. [ 36 ] Moreover, given the importance of proinflammatory mediators in shaping the immunosuppressive microenvironment (e.g., neutrophils well recognized as myeloid‐derived suppressor cells) both in the primary tumor and premetastatic niche, our findings can be used to explore potential synergy with immunotherapy, which is the focus of our current research.…”

Comparison between de novo and metachronous metastatic breast cancer: the presence of a primary tumour is not the only difference—a Dutch population-based study from 2008 to 2018

“…First, therapy choices are partly determined by the variable of interest (de novo versus metachronous MBC in uences therapy choices) and are therefore not a confounder but an intermediary variable. Second, speci cally in de novo MBC a RCT reported that local therapy of the primary tumour did not improve OS [10,11], so local therapy is not a confounder either. Likelihood ratio tests of Cox PH models were used to compare OS between the groups.…”

“…For instance, in de novo MBC the best approach regarding the primary tumour is still unclear. Many studies suggested an overall survival (OS) bene t of local treatment [7][8][9], but recent randomized studies have refuted this [10,11]. Unlike patients with de novo MBC, many patients with metachronous MBC have already received (neoadjuvant or adjuvant) systemic treatment in addition to loco-regional treatment following diagnosis of the primary tumour.…”