Julia R. White, MD, Professor of Radiation Oncology at The Ohio State University, Columbus, and the invited discussant of E2108, put these findings into context with three important studies evaluating the benefit of locoregional therapy for de novo stage IV breast cancer: the study from Tata Memorial in Mumbai,1 the Turkish Federation MF07-01 trial,2 and the Austrian ABCSG-28 POSYTIVE trial.3 E2108 and the Mumbai study treated all patients with systemic therapy first, then randomly assigned them to locoregional therapy; the Turkish and Austrian trials randomly assigned patients with operable tumors at presentation.
Although the studies are similar in many ways and different in others, their overall conclusions were consistent: the routine use of locoregional therapy cannot be recommended, according to Dr. White. The Turkish trial did show a survival benefit at 5 years, but not at 3 years; patients with multiple visceral metastases treated with local therapy actually had worse 3-year survival, but those with solitary bone metastases had better survival, she noted.
Clinical Implications
“Based on these four trials, should patients with primary intact tumors always have primary surgery for de novo metastatic breast cancer? Clearly, the answer is no,” said Dr. White. “None of the trials met the primary endpoint of improving overall survival.”
Dr. White continued: “Should this approach be used sometimes? Based on these trials, the answer is yes. Some patients (up to 20%) will have locoregional symptoms or disease progression that will need a surgical approach for palliation.”
Dr. White did propose one role for routine locoregional treatment: as a strategy in de novo oligometastatic breast cancer, where there are up to four operable distant metastases. Local therapy in combination with systemic therapy plus ablative therapy might render such patients with no evidence of disease and potentially cure them, she explained. This subject is the focus of ongoing clinical investigation.
DISCLOSURE: Dr. White reported no conflicts of interest.
REFERENCES
1. Badwe R, Hawaldar R, Nair N, et al: Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: An open-label randomised controlled trial. Lancet Oncol 16:1380-1388, 2015.
2. Soran A, Ozmen V, Ozbas S, et al: Randomized trial comparing resection of primary tumor with no surgery in stage IV breast cancer at presentation: Protocol MF07-01. Ann Surg Oncol 25:3141-3149, 2018.
3. Fitzal F, Bjelic-Radisic V, Knauer M, et al: Impact of breast surgery in primary metastasized breast cancer: Outcomes of the prospective randomized phase III ABCSG-28 POSYTIVE trial. Ann Surg 269:1163-1169, 2019.
