Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108)

Author(s): Seema A. Khan, MD, MPH1; Fengmin Zhao, MS, MHS, PhD2; Lori J. Goldstein, MD3; David Cella, PhD4; Mark Basik, MD5; Mehra Golshan, MD, MBA6;
Source: DOI: 10.1200/JCO.21.02006 Journal of Clinical Oncology Published online January 07, 2022. PMID: 34995128
Lucio Gordan MD

Dr. Lucio Gordan's Thoughts

Benefit of locoregional control seems limited probably to situations in which surgery could clearly help recurrent breast inflammatory/infectious issues. This study is helpful to quote to patients who are anxious about not having breast surgery accomplished in this setting.



Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results.


Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray’s test. Quality-of-life assessment used standard instruments.


Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms.


Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

Author Affiliations

1Northwestern University, Chicago, IL;; 2Dana Farber Cancer Institute—ECOG-ACRIN Biostatistics Center, Boston, MA; 3Albert Einstein Medical Center, Philadelphia, PA; 4Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; 5Jewish General Hospital Lady Davis Institute, McGill University, Montréal, QC, Canada; 6Yale School of Medicine, Yale Cancer Center, New Haven, CT; 7The Allegheny Health Network Cancer Institute, Pittsburgh, PA; 8Mayo Clinic, Phoenix, AZ; 9Swedish Medical Center, Seattle, WA; 10University of Oklahoma Health Sciences Center, Oklahoma City, OK; 11Montefiore Medical Center, Bronx, NY; 12University of Texas MD Anderson Cancer Center, Houston, TX; 13Eisenhower Medical Center, Rancho Mirage, CA; 14Case Western Reserve University, Cleveland, OH; 15Indiana University School of Medicine, Indianapolis, IN; 16University of Wisconsin Carbone Cancer Center, Madison, WI; 17Wake Forest University Health Sciences, Winston Salem, NC; 18Stanford University School of Medicine, Stanford, CA

1 thought on “Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108)”

  1. Luis Carrascosa

    This should be interpreted with caution. It definitely makes sense for uncomplicated breast tumors, however, if there is evidence of local progression before, during or after systemic therapy such as tumor eroding through skin, bleeding, pain, infections, etc, local therapy with either surgery or radiation should be seriously considered as it significantly improves quality of life. By avoiding locoregional complications the patient will be able to continue systemic therapy without interruptions.

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