SAN ANTONIO—Women who present with metastatic breast cancer who respond to front-line chemotherapy should not routinely be offered locoregional treatment of the primary tumor and axillary nodes, a prospective randomized controlled trial presented at the 2013 San Antonio Breast Cancer Symposium has found.
Not only is there lack of a survival benefit, “surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases,” said Rajendra Badwe, MD, of the Tata Memorial Hospital in Mumbai, India.
“I’m sure a lot of oncologists who believe in conventional wisdom and don’t provide locoregional treatment will feel a lot more comfortable looking at these results,” he said. “As for those who have changed practice based on the retrospective study history, they would have to rethink.”
Dr. Badwe explained the role of locoregional treatment in women presenting with metastatic breast cancer—from 5% to 20% worldwide—is the subject of debate. Preclinical evidence, for example, “suggests such treatment may facilitate growth of metastatic disease. On the other hand, many retrospective analyses in clinical cohorts have suggested favorable impact of locoregional treatment in these patients.”
Noting these results are likely influenced by selection bias, Dr. Badwe and colleagues conducted a study to assess the effect of locoregional treatment on outcome in women with metastatic breast cancer at initial diagnosis. Between February 2005 and January 2013, 350 women who had objective tumor response after six cycles of anthracycline-based chemotherapy were randomly assigned to locoregional treatment (n = 173) or no locoregional treatment (n = 177). Patients were stratified by receptor status, site of metastases (visceral vs. bone vs. both).
In the locoregional treatment arm, per standard adjuvant guidelines, women received breast conserving surgery or mastectomy plus axillary lymph node dissection followed by radiation therapy. In the no locoregional treatment arm, women were simply followed; all women received regular clinical evaluation. After the last cycle of chemotherapy, all women received standard endocrine therapy, if indicated. Imaging was performed within 6 months postrandomization and thereafter, as indicated.
Baseline demographic characteristics were balanced between the two arms with respect to age, clinical tumor size, HER2-receptor status, and stratification factors. Eight patients (5.8%) in the locoregional treatment arm did not undergo treatment and 19 patients (10.7%) in the no-locoregional treatment arm “underwent surgical removal of primary tumor because of palliative reasons,” he said.
At a median follow-up of 17 months, 218 deaths had been recorded, 111 in the locoregional treatment are and 107 in the arm without locoregional treatment.
Median overall survival (OS), the primary end point, was 18.8 months in the locoregional treatment arm and 20.5 months in the arm without locoregional treatment (hazard ratio [HR], 1.07; 95% CI: 0.82-1.40; P = 0.60). Corresponding 2-year OS rates were 40.8% and 43.3%, respectively.
At 72 months, OS was 19.2% in the locoregional treatment arm and 20.5% in the arm without locoregional treatment (HR, 1.04; 95% CI: 0.80-1.34; P = 0.79).
After adjusting for age, ER status, HER2-receptor status, site of metastases, and number of metastatic lesions in a Cox regression model, no significant difference in OS between the arms was observed (HR, 1.00; 95% CI: 0.76-1.33; P = 0.98). There was no interaction between the effect of locoregional treatment and covariates in the model.
“We were unable to identify any subgroups that are likely to benefit from locoregional treatment,” Dr. Badwe concluded. “Such treatment should be reserved for women who need it for palliative reasons.”
- Badwe R et al. S2-02. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.