Locoregional treatment does not improve outcomes in women with stage IV breast cancer

Reviewed by Emily Henderson, B.Sc.Feb 17 2022

Treating a tumor in the breast when distant metastases have already occurred does not improve outcomes in women with stage IV breast cancer, according to a new study published in the Journal of Clinical Oncology.

Retrospective studies of treatment outcomes had suggested there was a benefit to treating the breast tumor, instead of only treating the metastases, which has long been standard practice, according to Seema Khan, MD, the Bluhm Family Professor of Cancer Research, interim co-vice chair of research in the Department of Surgery and lead author of the study.

"It's possible that some subset of patients will derive a benefit from treatment of the breast tumor, but we were unable to identify such a subset in our trial, so this remains hypothetical," said Khan, who is also a professor of Surgery in the Division of Breast Surgery and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Stage IV breast cancer is defined by cancer recurrence in a distant organ, or as occurs in about 6 percent of newly diagnosed breast cancer patients, when a patient is first diagnosed with breast cancer after it's spread to other parts of the body.

These women typically come in with bone pain or some other symptom, and when the symptom is investigated, we discover that it is caused by spread of a cancer and then the original tumor in the breast is identified."

Seema Khan, MD, the Bluhm Family Professor of Cancer Research

These patients are usually treated with anti-cancer drugs targeting the distant metastases. The breast tumor is left alone, as the disease in locations outside the breast is more dangerous. However, some retrospective studies showed better survival in women who also received locoregional treatment (surgery, radiation or both) for the breast tumor alongside treatment for the cancer in other places.

In the current trial, 256 women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for four to eight months. If no disease progression occurred, they were randomly assigned to locoregional therapy for the breast tumor (surgery and radiotherapy) or continuing systemic therapy.

Overall survival after three years was 67.9 percent without and 68.4 percent with early locoregional therapy — an improvement that was not significant. Further, investigators expected to see some quality-of-life improvements in the locoregional treatment arm, as previous studies have shown that growth of the tumor in the breast can negatively impact quality of life, but quality of life measurements were largely similar between the two groups of patients.

"It appears the positive effects of tumor removal were not greater than the negative quality of life generated by the presence of the breast tumor," Khan said. "This is probably related to the bodily injury caused by surgery or radiation, which can have some long-lasting effects."

While the results are disappointing, they contain an important lesson about retrospective studies. Critical for understanding health and generating hypotheses, retrospective trials do suffer from many types of bias — in this case, selection bias, according to Khan.

"Someone in better overall condition may have been offered surgery for the breast tumor, while only the distant tumor was treated for someone in worse condition," Khan said. "This is one of the cases where the retrospective studies were helpful, but the discussion can only be settled with a randomized trial."