Late Breaking Abstract – ASCO 2020: Local Therapy Does Not Extend Survival in Newly Diagnosed Metastatic Breast Cancer

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (13%) will develop invasive breast cancer during their lifetime. Approximately 276,480 new cases of invasive female breast cancer will be diagnosed in 2020 and about 42,170 women will die of the disease. Approximately 6% of newly diagnosed breast cancer patients present with Stage IV disease. Breast surgery is often not a consideration for patients with metastatic breast cancer. However, breast surgery can be offered for palliation of symptoms, taking into consideration the risks and benefits of such intervention, in a patient with an ulcerated, bleeding, or a fungating tumor mass, that cannot be controlled with systemic therapy. It has been hypothesized based on retrospective analyses, that the addition of surgical resection of the primary tumor in the breast, to systemic therapy, in patients presenting with Stage IV disease, improved survival. Randomized clinical trials however have provided conflicting results.

E2108 is a randomized, Phase III trial which evaluated the benefit of locoregional treatment for the intact primary breast tumor, following initial systemic therapy, in newly diagnosed breast cancer patients presenting with Stage IV disease. In this study, 256 eligible patients with de novo metastatic disease, who did not progress during a 4-8 months period, while on optimal systemic therapy based on patient and tumor characteristics, were randomized to either continue systemic therapy alone (N=131) or combine it with locoregional therapy such as surgery and radiation for the intact primary breast tumor (N = 125). Of the 125 patients who received early locoregional therapy, 109 patients underwent surgery of whom 87 had free margins and 74 patients received locoregional radiation therapy. The Primary endpoint was Overall Survival (OS), and Secondary endpoint was locoregional disease control.

At a median follow up of 59 months, there was no significant difference in Overall Survival (OS) between the optimal systemic therapy plus locoregional therapy compared with optimal systemic therapy alone (3-year OS rate was 68.4% versus 67.9%; HR=1.09; P=0.63). Further, the addition of locoregional therapy to systemic therapy, also failed to improve 3-year Progression Free Survival (P=0.40). There was however significantly higher locoregional recurrence or progression in the systemic therapy alone group compared with the systemic therapy plus locoregional therapy group (3-year rate 25.6% versus 10.2%, P=0.003). Health-related Quality of Life measures such as depression, anxiety and well-being were significantly worse in patients who underwent systemic therapy plus locoregional therapy, compared with systemic therapy alone.

The authors concluded that for patients with a new diagnosis of breast cancer presenting with Stage IV disease, surgery and radiation for the primary breast tumor should not be offered, with the expectation of a survival benefit.

A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: a trial of the ECOG-ACRIN Research Group (E2108). Khan SA, Zhao F, Solin LJ, et al. J Clin Oncol 38: 2020 (suppl; abstr LBA2)