Women who present at diagnosis with advanced breast cancer have faced an unanswered question: will local therapy, consisting of surgery and radiation to the tumor in the breast, prolong survival compared to the traditional treatment of systemic treatment alone?

Now, data from the randomized phase III E2108 trial showed that the survival experience of the two treatments was the same—local therapy did not improve overall survival. The goal of the study was to determine whether surgery and radiation should become routine practice for patients with stage IV breast cancer and resolve conflicting data from two earlier randomized trials. Findings from the trial were highlighted in the Plenary Session of the ASCO20 Virtual Scientific Program (Abstract LBA2) and presented by Seema A. Khan, MD, and colleagues.

“Based on the results of our study, women who present with a new diagnosis of breast cancer already in stage IV should not be offered surgery and radiation for the primary breast tumor with the expectation of a survival benefit."

— Seema A. Khan, MD

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“Based on the results of our study, women who present with a new diagnosis of breast cancer already in stage IV should not be offered surgery and radiation for the primary breast tumor with the expectation of a survival benefit,” said lead investigator Dr. Khan, of Northwestern University, in a statement. “When making these decisions, it is important to focus energy and resources on proven therapies that can prolong life.”

Study Background

About 1 in every 20 women diagnosed with breast cancer in the United States each year present with metastatic cancer. Patients with stage IV breast cancer usually receive systemic treatment such as chemotherapy, targeted therapy, hormone therapy, or immunotherapy.

Traditionally, it was thought that because metastases had occurred, local therapy would not provide any additional survival benefit beyond what systemic treatment could offer. Starting about 20 years ago, this approach was questioned based on the idea that the primary tumor could be a source of reseeding of cancer outside the breast. Several studies suggested that removal of the tumor in the breast with surgery would be beneficial; further complicating matters, two randomized clinical trials published in the past 5 years had conflicting results. E2108 was launched in order to provide definitive answers to these questions.

Study Details and Results

In E2108, 390 women with stage IV breast cancer were enrolled. All received the optimal systemic treatment for them based on the number of other organ systems involved and tumor biomarker status. Of those whose disease responded to initial systemic therapy, or stayed stable, 256 women agreed to be randomly assigned to either continue with systemic therapy or to receive surgery and radiation and then continue on with systemic treatment.

The results show that there was no significant difference in overall or progression-free survival between the two groups (3-year overall survival rate = 68.4% in the optimal systematic therapy plus locoregional treatment arm vs 67.9% in the optimal systemic therapy alone arm).

“When combined with the results of an earlier trial in Mumbai, India [published by Badwe et al in The Lancet Oncology], these results tip the scales against the possibility that local therapy to the breast tumor will help women live longer,” said Dr. Khan. “The Indian trial had a similar design to E2108, and also showed similar results between the two treatment groups.”

The E2108 trial also compared patient-reported quality of life between the two groups. It found that there was no quality-of-life advantage in the group of women who received local therapy to the breast tumor.

“This result was a little surprising since one of the reasons for considering surgery and radiation is the idea that growth of the tumor will impair quality of life,” said Dr. Khan. “Instead, we find that the adverse effects of surgery and radiation appear to balance out the gains in quality of life that were achieved with better control of the primary tumor.”

The study authors concluded, “Early local therapy does not improve survival in patients with de novo metastatic breast cancer and an intact primary tumor. Although there was a 2.5-fold higher risk of local disease progression without locoregional treatment, locoregional treatment of the intact primary tumor did not lead to improved health-related quality of life.”

Disclosure: The ECOG-ACRIN Cancer Research Group designed and led this trial, which was conducted in the National Cancer Institute National Clinical Trials Network with funding from the National Cancer Institute, part of the National Institutes of Health. For full disclosures of the study authors, visit coi.asco.org.