Improved Survival With Surgery in Metastatic Breast Cancer

Selected patients with metastatic breast cancer at diagnosis had significantly better survival with surgery in addition to systemic therapy, an analysis of almost 13,000 patients showed.

Overall, the survival hazard improved by 27%-36% in women with known receptor status (estrogen, progesterone, and HER2) treated with systemic therapy plus surgery with or without radiation therapy. Women with HER2-positive tumors had a 5-year overall survival (OS) of 48% with trimodal therapy, 41% with surgery and systemic therapy, and 29% with systemic therapy alone (P<0.0001).

The largest survival benefit occurred in women who received neoadjuvant chemotherapy, as opposed to adjuvant therapy, reported Chan Shen, PhD, of Pennsylvania State University College of Medicine in Hershey, and colleagues, in the Annals of Surgical Oncology.

“In contrast to the results of other analyses, our findings were focused on a population of patients whose hormone receptor and HER2 status were known,” the authors stated. “The responses of stage IV breast cancer patients with various treatment regimens stratified and analyzed by biologic subtypes has not been reported previously.”

“In addition, by excluding patients who died within the first 6 months after diagnosis due to very advanced disease or aggressive biology, our analysis is more representative of the effect that different treatment methods have on survival when patients have treatment-responsive metastatic breast cancer.”

About 6% of breast cancers are metastatic at diagnosis. The disease remains incurable, but treatment advances, particularly systemic therapies, have significantly improved survival over the past decade, the authors noted. Systemic therapies continue to form the basis of treatment for metastatic breast cancer.

Multiple studies have examined the impact of surgery to the primary tumor on outcomes in metastatic breast cancer, and the results reported to date have been conflicting. Most recently, a randomized trial of systemic therapy with or without surgery showed no difference in progression-free survival with the addition of surgery to the primary tumor.

Despite the conflicting data, 20%-40% of patients with stage IV breast cancer undergo surgery to the primary tumor or metastases, the authors noted. The rates are higher than would be expected for symptom palliation, which is what the National Comprehensive Cancer Network recommended during the period studied.

Prior studies of surgical intervention in metastatic breast cancer did not consider hormone receptor or HER2 status or the sequence of chemotherapy (neoadjuvant vs adjuvant) in relation to surgery. Shen and colleagues addressed those issues in a query of the National Cancer Database to identify women with newly diagnosed stage IV breast cancer during 2010 to 2015.

The analysis included 12,838 patients with known hormone receptor (ER and PR) and HER2 status. Patients who died within 6 months of diagnosis were excluded. The primary endpoint was 5-year OS.

The data showed that 6,649 patients received systemic therapy alone, 2,906 received systemic therapy plus radiation therapy, 1,689 received systemic therapy plus surgery, and 1,594 received trimodal therapy. For the period reviewed, use of systemic therapy plus or minus radiation therapy increased, whereas use of surgery and trimodal therapy decreased.

Patients with hormone receptor-positive breast cancer were significantly more likely to be treated with systemic therapy alone or with radiation therapy (estrogen: 73.1% and 80.7% vs 64.9% and 68.4% for surgery and trimodal therapy, P<0.001; progesterone: 60.9% and 66% vs 52.5% and 57.0%, P<0.001). HER2-positive tumors accounted for 23%-29% of tumors across the four treatment groups.

For the entire cohort, trimodal therapy and systemic therapy plus surgery led to higher 5-year OS: 38% for trimodal, 32% for surgery and systemic therapy, 21% for systemic therapy alone, and 19% for systemic therapy plus radiotherapy (P<0.001). The HER2-positive subgroup not only had better 5-year OS with surgery or trimodal treatment, but had higher OS than the entire cohort, regardless of treatment.

Investigators examined the sequence of systemic therapy in a subgroup of 3,283 patients who underwent surgery. Patients with HER2-positive tumors had significantly higher 5-year OS with neoadjuvant therapy (55%) than with adjuvant therapy (35%), as well as patients who had HER2-negative tumors treated with adjuvant therapy (30%, P<0.001).

With regard to hormone receptor status, neoadjuvant chemotherapy led to better 5-year OS across the board (P<0.0001):

• ER-positive: 42% vs 30% with adjuvant chemotherapy
• ER-negative: 30% vs 22%
• PR-positive: 45% vs 32%
• PR-negative: 32% vs 25%

“Surgery in addition to ST [systemic therapy] has a survival benefit for stage IV breast cancer patients with known hormone receptor and HER2 status and should be considered after NAC [neoadjuvant chemotherapy] for patients with ER-positive, PR-positive, or HER2-positive disease,” the authors concluded.