Impact of breast surgery in de novo stage IV breast cancer

The article, entitled “Impact of Breast Surgery in Primary Metastasized Breast Cancer Outcomes of the Prospective Randomized Phase III ABCSG-28 POSYTIVE Trial”, published in the Annals of Surgery (1), is the third to study to prospectively evaluate the prognostic efficacy of breast surgery in patients with metastases (Table 1). This trial evaluated breast surgery for newly diagnosed de novo stage IV breast cancer patients with no history of systemic therapy. After providing informed consent, patients were allocated to arm A (surgery consisting of either standard breast-conserving surgery or mastectomy including axillary staging and systemic therapy) or to arm B (systemic therapy without surgery). The patients were stratified according to grading, receptor status, HER2 status, metastasis location (visceral vs. bone-only metastases) and planned first-line therapy. As systemic therapy, chemotherapy, anti-HER2 therapy, or anti-hormone therapy was administered according to local standards, with regimens including modern effective drugs. The primary endpoint was overall survival (OS) and the authors reported that they could not demonstrate a prognostic benefit for primary tumor resection. Additionally, they reported worsening of the outcomes of the patients with distant metastasis. The time to distant progression in the surgery arm was shorter (though not significantly) than that in the no-surgery arm (HR 0.598, 95% CI, 0.343–1.043; P=0.0668). These results were very similar to those of the first report on a prospective trial from India (2) but different from the results of many retrospective reports (3). In our view, the limitation of systemic therapies is one of the reasons for this discrepancy. In the Indian trial, the patients did not receive systemic therapies according to breast cancer subtypes. Anti-HER2 targeted therapies were not used for patients with HER2-positive subtype, and very few patients with ER-positive tumors received hormone therapy. In addition, the discontinuation of effective systemic therapy after randomization might result in a poorer outcome, especially distant progression free survival, in the patients with primary tumor resection. However, the patients received modern and continuous systemic therapy in this ABCSG trial and the results were similar to those of prior trials. Given these results, it appears that stage IV breast cancer patients should not undergo primary tumor surgery