ABSTRACT: Approximately 5% of primary breast cancer patients present de novo stage IV breast cancer, for whom systematic therapy is the mainstream treatment. The role of surgical excision of the primary tumor has been controversial due to inconsistent results of relevant studies. Recently, with the reports of some relevant preclinical data, retrospective studies and randomized clinical trials, we've got more evidence to reexamine the issue. Based on those above, a literature review and meta-analysis was performed to determine whether surgery of the primary tumor could improve overall survival in the setting of stage IV breast cancer.A comprehensive search of PubMed, OVID, American Society of Clinical Oncology (ASCO) symposium documents, European Society for Medical Oncology (ESMO) symposium documents and San Antonio Breast Cancer Symposium (SABCS) symposium documents was performed to identify published literature that evaluated survival benefits from excision of the primary tumor in the setting of stage IV breast cancer. Data were extracted in review of appropriate studies by the authors independently. The primary endpoint was overall survival following surgical removal of the primary tumor. Secondary endpoints were the impacts of surgery on progression free survival (PFS) and time to progression (TTP).Data from 19 retrospective studies showed a pooled hazard ratio of 0.65 (95% confidence interval (95% CI), 0.60-0.71, P < 0.01= for overall survival (OS), indicating a 35% reduction in risk of mortality in patients who underwent surgical excision of the primary tumor. Nevertheless, the analysis of 3 randomized clinical trials revealed a pooled hazard ratio of 0.85 (95% CI, 0.59-1.21, P = 0.359) for OS in the surgical group. According to the meta-regression, the survival benefit was independent of age, tumor size, site of the metastases, and PR or HER-2 status, acceptance of systematic therapies and radiotherapy and inversely correlated with the ER+ status of the population included.This is the first meta-analysis that includes both retrospective and prospective studies regarding the impact of surgery of the primary tumor on survival in stage IV breast cancer patients. According to the analytical results, we do not recommend surgery of the primary tumor as routine therapy for stage IV breast cancer. However, for those who are supposed to have long life expectancy, physicians could discuss it with these patients, put forward surgery as a therapy choice and perform the operation under deliberation.
