Surgery of primary tumors in stage IV breast cancer: an updated meta-analysis of published studies with meta-regression

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Abstract
Systemic therapy is the mainstream treatment of stage IV breast cancer. Surgical excision of the primary breast cancer tumor in the presence of synchronous metastatic disease is debated, but a shared indication is not proposed by current guidelines. The purpose of this analysis is to aggregate the published survival data of surgery of an intact primary tumor in stage IV disease. The authors searched PubMed for publications reporting data about the survival benefit of surgery of the primary tumor in patients with metastatic breast cancer. Hazard ratios for survival when reported after multivariate analysis (with 95 % confidence intervals) were obtained from publications and pooled in a meta-analysis. A meta-regression weighted for the extent of disease, ER/HER2 status, age, visceral or bone disease, rate of radiotherapy, and systemic therapies offered was performed. A total of 15 publications were included in this meta-analysis. Surgery of the primary tumor appeared to be an independent factor for an improved survival in the multivariate analyses from the individual studies, with an HR of 0.69 (p < 0.00001). According to meta-regression, the survival benefit was independent of age, extent, site of the metastatic disease, and HER2 status, but was directly proportional to the rate of patients exposed to systemic therapies and radiotherapy and inversely correlated with the ER+ status of the population included. Surgery of the primary tumor in stage IV breast cancer seems to offer a survival benefit in metastatic patients, in particular when it is offered in a multimodality treatment program.

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