Surgery of the Primary Tumor in De Novo Metastatic Breast Cancer Confers No Survival Benefit

Abstract

The benefit of locoregional therapy (LRT) for de novo metastatic breast cancer (dMBC) has been challenged in the past through various retrospective and prospective audits. Many of these studies reported that younger women with hormone receptor-positive (HR?) disease, fewer sites of metastasis, and bone-only metastasis appeared to benefit from local control. This benefit could be attributed to a consistent bias in patient selection for these studies. Over the years, four randomized trials (RCTs) have addressed the role of surgery in dMBC. Three of these studies and the recently published meta-analysis have reported no survival benefit with LRT in dMBC. Despite this, Stahl et al. have again presented a retrospective review of patients questioning the role of LRT in specific subgroups. This retrospective review, as with most retrospective audits, had a selection bias due to inclusion of patients who had low metastatic burden, with 52% to 70% exhibiting single site or oligometastatic disease at presentation. Also, in their allusions to the Tata Memorial Centre trial, Stahl et al. have misrepresented the study because they have incorrectly suggested that only 10% of the included patients had received primary systemic therapy. That trial was a prospective RCT designed to address the benefit of LRT after primary systemic therapy for dMBC patients with a relatively higher tumor burden. All the patients included in the TMH trial had received standard systemic therapy as per institutional protocol, and the responders (i.e., 350 women) were randomized to either undergo further locoregional therapy or not receive the therapy. Additionally, the authors have suggested that the primary tumor is a possible source of circulating tumor cells and that the removal of such a source may improve survival. However, the ABCSG-28 POSYTIVE trial and the Tata Memorial trial reported that LRT was associated with a significantly worse time to distant progression, which is consistent with the results of the preclinical studies. These results suggest that an accelerated growth of metastases could possibly occur after removal of the primary tumor and could be detrimental to the patient. Based on randomized evidence, we know that LRT in dMBC offers no survival advantage despite significant improvement in locoregional control. Any retrospective analysis is fraught with selection bias and therefore is not reliable for changing clinical practice and should be interpreted with caution.