The Survival Benefit of Local Surgery in Stage IV of Breast Cancer

Treatment of Metastatic Breast Cancer is not usually considered curative. Recent retrospective studies have demonstrated that resection of the breast tumor in patients with primary metastatic breast cancer is associated with a significant improvement of the prognosis. In all these aforementioned studies, the decision to perform surgery could have been influenced by favorable prognostic factors, such as younger age, the presence of only one metastatic site, or good response to systemic therapy. To rule out the impact of potential confounders, most studies adjusted for age, tumor size, number and sites of metastases and hormone receptor status. In addition, some studies also adjusted for comorbidity or surgical margins. For example, in the study of Bafford et al., the benefit of surgery seemed confined to patients operated upon before diagnosis of metastatic disease and there was no survival advantage in patients who received an operation of the breast tumor after the diagnosis of the metastatic disease had taken place. This phenomenon was referred to as the stage migration bias. In a study by Leung et al., the benefit from surgery disappeared in the multivariate analysis when taking into account the use of chemotherapy. Finally, in a study by Cady et al. coding errors in the retrospectively collected dataset were found to explain part of the survival advantage. 4Therefore, this randomized controlled trial (RCT) has been initiated.

In the literature, several retrospective studies noted that 35-60% of patients with metastatic cancer at the time of diagnosis received local treatment of primary lesions, which resulted in a positive impact on survival. However, an analysis of 16,023 patients presenting with stage IV disease and an intact primary tumor compared outcomes between patients having surgery of the primary tumor to negative margins or no surgery. In a multivariate analysis adjusting for known prognostic factors, surgery reduced the HR for death to 0.61 (95% CI = 0.58 to 0.65). Multiple other retrospective studies from single institutions, registries, and population-based cohorts have confirmed this initial observation, but it is uncertain whether these studies reflect a real benefit for surgery or consistent selection bias. Three prospective randomized trials are examining the role of surgery in patients presenting with stage IV disease and an intact primary tumor. While awaiting the results of these trials, it is not known precisely how or when to integrate such surgical management into a standard medical therapy for metastatic breast cancer or which patients, in particular, are most likely to benefit from such treatment. 1 The aim of this study is to investigate the effect of surgery of the primary tumor in breast cancer patients with distant metastatic disease at initial diagnosis. According to the controversies in previous studies design of a study with the least confounding factor to decrease the bias seems to be necessary.