Local therapy does not improve survival for de novo metastatic breast cancer

A randomized trial of women with de novo metastatic breast cancer found that surgery and radiation to remove the primary tumor did not lead to longer survival. The study was presented on May 31 as part of the ASCO Annual Meeting.

Background

According to the researchers who authored this study, about 6 percent of breast cancer diagnoses in the United States are de novo metastatic. This means the cancer was metastatic when it was first diagnosed. For all metastatic breast cancers, including those diagnosed de novo, the current recommended care is systemic therapy — chemotherapy or targeted therapy medicines — to treat the cancer throughout the body.

In the past, researchers have questioned whether that standard is correct. Some have suggested that surgery to remove the primary tumor in the breast could stop it from spreading cancer cells that form metastases in other parts of the body.

Results from retrospective studies — studies that look back on collected data — have suggested that this approach could cause people to live longer. But there has not been clear data from controlled trials to show whether local therapy can improve overall survival. Trial E2108, run by the ECOG-ACRIN Research Group, aimed to answer this question with a randomized trial.

This study enrolled 390 women with de novo metastatic breast cancer. All began treatment with the recommended systemic therapy for their diagnosis. The 256 women whose cancer did not grow after 4 to 8 months of treatment were randomly assigned to

• continue systemic therapy uninterrupted (131 women)
• get local treatments before continuing on systemic therapy (125 women)

The main goal of the study was to see if local treatment led to people living longer than they would with systemic therapy alone. It also studied if people getting local treatment went longer without cancer progressing, if they had better health-related quality of life, and if there were fewer progressions in the breast that was treated.

Results

Local therapy did not cause people to live longer or go longer without cancer growing. The overall survival and progression-free survival results were the same for both groups, with an median overall survival of 54 months.

Of note, people on local therapy did not report improved quality of life over those who got systemic therapy. Those who got local therapy had better quality of life at 18 months into the study, but had similar quality of life to people who got systemic therapies at all other times participants were surveyed.

Researchers looked specifically at people with different breast cancer subtypes and also found no overall survival difference between local and systemic therapy in women with HER2-positive breast cancer or hormone receptor-positive breast cancer. The overall survival was worse for local therapy in women with triple-negative breast cancer, but with only 20 women in this group, the results could be by chance.

The only measure where local therapy had results that were better than systemic treatment was with cancer control within the breast:

• 25.6 percent of women assigned to systemic therapy later had surgery to manage the symptoms of cancer growth in the breast.
• 10.2 percent of women assigned to local therapy had cancer growth in the breast, chest, or nearby lymph nodes.

What this means for you

Julia R. White, MD, of The Ohio State University Comprehensive Cancer Center, who led a discussion on this study noted that these results, supported by results from three previous studies, show that local treatment should not be offered to people with de novo metastatic breast cancer with the hopes of improving survival. Your doctor may still recommend surgery or radiation to treat the breast to manage specific issues in the breast such as pain and discomfort caused by that tumor.

Systemic therapy has long been the standard of care and the recommended treatment for those diagnosed with de novo metastatic breast cancer. This study supports the continued use of chemotherapy, targeted therapy, and other medicines that treat cancer throughout the body.

Studies that fail to meet their goals are often seen as failures, but they help us understand how treatments work and when they don’t. This study also helps clarify the goals of surgery in metastatic breast cancer; that researchers included health-related quality of life gives information to help you weigh the risks and benefits of having surgery. Though these results will not change treatment, the information they provide is important in understanding the best treatments for every diagnosis.