Does early surgery improve survival among women with de novo metastatic breast cancer and an intact primary tumor? According to the results of a recent international, multi-center investigation, the answer is no.

The researchers behind the study concluded that overall survival did not differ between patients who did and did not receive early locoregional therapy in conjunction with optimal systemic therapy. 

Reporting online in an abstract presented to the 2020 virtual meeting of the American Society of Clinical Oncology (abstract LBA2), the investigators explained that some 6% of patients with newly diagnosed breast cancer present with stage IV disease and an intact primary tumor. 

“Locoregional treatment for the intact primary tumor is hypothesized to improve survival based on retrospective analyses, but randomized trials have provided conflicting data,” the authors wrote. 

Given these contradictions, the investigators set out to examine the safety and efficacy of locoregional treatment for the intact primary tumor following initial systemic therapy (NCT01242800).

As part of the phase-three trial, 390 adult patients (≥18 years) with stage IV metastatic breast cancer and an intact primary tumor were enrolled. These individuals were treated with optimal systemic therapy according to both patient and tumor characteristics. Patients who did not progress during the first four to eight months of optimal systemic therapy were randomized to either locoregional treatment for the intact primary tumor or no locoregional treatment. 

The study’s primary endpoint was overall survival. Secondary endpoints included locoregional disease control and health-related quality of life.  

Patients were enrolled between February 8, 2011 and July 23, 2015; all received optimal systemic therapy. Of these, 256 eligible patients were randomized to either continued optimal systemic therapy alone (n=131) or optimal systemic therapy plus locoregional treatment (n=125).

In total, the study found 121 deaths and 43 locoregional progression events after a median follow-up period of 59 months (range: 0-91 months). Nevertheless, no significant differences were found between groups with respect to overall survival. Indeed, the three-year overall survival rate was 68.4% among women who received optimal systemic therapy plus locoregional treatment, compared with 67.9% among their counterparts who received only optimal systemic therapy (hazard ratio 1.09; 90% confidence interval: 0.80-1.49; p=0.63).

Similarly, no statistically significant differences were found between the two treatment groups with respect to progression-free survival (p=0.40). 

On the other hand, patients who received optimal systemic therapy alone demonstrated significantly greater rates of locoregional recurrence/progression (25.6%) than did those who received optimal systemic therapy plus locoregional therapy (10.2%; p=0.003). 

Despite these differences, however, health-related quality of life -- as measured by the FACT-B Trial Outcome Index -- was significantly worse among women in the optimal systemic therapy plus locoregional treatment arm at 18 months after randomization (p=0.01). Similar differences were not observed between groups at either six months or 30 months, however.

In light of these findings, the investigators concluded that 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 therapy,” the authors concluded, “locoregional treatment of the intact primary tumor did not lead to improved health-related quality of life.”  

The study was funded by the Eastern Cooperative Oncology Group.