Intervention in Metastatic Breast Cancer Benefits Subset of Patients

LAS VEGAS—A subset of breast cancer patients with metastases in the lung and/or liver may benefit from surgical or ablative intervention, according to a recent study. A hypothesis constantly discussed is whether intervention at the metastatic site will slow or avert systemic spread by eliminating resistant clones. Researchers in a recent study further hypothesized that surgical intervention may also eliminate reseeding from the metastatic site.

“The development of systemic therapy has increased survival in the metastatic setting by 1% to 2% per year, and better imaging technology has allowed us to detect smaller tumor burdens, resulting in less morbid interventions,” said Attila Soran, MD, MPH, a professor of clinical surgery at the University of Pittsburgh Medical Center.

Dr. Soran and his co-investigators conducted a multicenter, prospective registry study of 200 patients diagnosed with metastatic tumors in the lung or liver (with or without bone metastases) after 2014. All patients had either hormone receptor–positive or HER2-positive tumors and up to five tumors in the lung, liver or both, with or without bone involvement. The patients were divided into two treatment groups: systemic therapy alone (ST) and intervention with systemic therapy (IT).

Overall, 116 patients (58%) had liver metastases with or without bone involvement, 101 (50%) had lung metastases with or without bone involvement, and 17 (8%) were affected at both sites with or without bone involvement. The majority, 150 patients (75%), had hormone receptor–positive disease and 64 (32%) had HER2-positive tumors.

Demographic characteristics were similar in the two groups, and median follow-up was 77 months in the IT group and 57 months in the ST group. Among 119 patients who received IT, 64 (32%) underwent surgical resection and 55 (27%) had metastatic ablative interventions.

“The hazard of death [HoD] was around 56% less in the IT group overall,” Dr. Soran reported. Specifically, HoD was lower in the IT group in patients less than 55 years of age and in patients with estrogen receptor/progesterone receptor (ER/PR)–positive, HER2-negative cancer.

“When we talk with patients, we are not always talking about overall survival. When metastases happen, patients want to know their survival after metastasis. This is why we look at the post–distant recurrence–-free survival,” Dr. Soran said. In the post-distant evaluation, HoD was 61% lower in the IT group than in the ST-only group. When the researchers analyzed the study in 2020, 76% of patients in the IT group were still alive, compared with 60% in the ST group.

“We are not saying that everybody has to get an intervention, but if you are considering overall survival or progression-free survival, there are some groups, such as patients younger than 55, those with ER/PR-positive or HER2-positive disease, oligometastases to lung or liver, and metastatic disease–free survival for more than 24 months, that you should discuss in tumor boards, including your surgeons from liver and lung,” Dr. Soran said.

Seema Khan, MD, a professor of surgery at Northwestern University Feinberg School of Medicine, in Chicago, commented that previous research on the resection of metastatic disease has been mainly retrospective, and that the addition of this prospective study is useful, reinforcing other analyses that also found a survival benefit with surgical or ablative intervention in metastatic disease. However, she had some questions about the data set.

“The authors defined oligometastatic disease as the presence of five or fewer lesions in the lung, liver or both. However, they also allowed patients with bony metastases to be registered, and there is no discussion of the fraction of patients who had bone metastases in addition to lung and liver disease. If bony disease was not subject to local therapy, this raises the question of whether all metastatic lesions were treated,” she said.

Dr. Soran replied that not all bone lesions received interventional treatment; the institutional tumor boards determined the treatment strategy for the bones. He also reminded that “limited metastasis is defined as a single resectable metastasis or fewer than five total metastases within surgical resection limits that can be resected with R0 resection of the lung and/or liver metastases.”

Dr. Khan also pointed out that although recent randomized controlled trials investigating stereotactic body radiotherapy (SBRT) have shown encouraging results, the use of radiotherapy was not detailed in the presentation. “Subsequent to the [American Society of Breast Surgeons] meeting in April, BR002 results were presented at [the American Society of Clinical Oncology]. This was a randomized phase 2 trial testing the addition of metastasis-directed local therapy to standard-of-care systemic therapy, and showed no advantage to the use of metastasis-directed local therapy. Therefore, this remains an open question that requires unbiased testing in a randomized fashion.”

Finally, Dr. Khan questioned the authors’ hypothesis that resection of limited metastatic disease decreases seeding of new sites from those lesions. “Many would argue that new metastatic sites are not seeded from existing metastases, but represent micrometastases that were resistant to postoperative adjuvant therapy and were derived from the primary tumor before it was resected,” she noted.