Anees B. Chagpar, MD, MSC, MPH, MA, MBA
Associate Professor of Surgery
Assistant Director of Global Oncology
Yale Comprehensive Cancer Center
New Haven, Connecticut
Patients with distant metastatic disease at presentation constitute 3% to 10% of patients with breast cancer. Historically, these patients have been considered to have systemic disease that cannot be treated with surgery for curative intent. This is often a devastating diagnosis for a patient, who is faced with only palliative options.
The rate of resection of primary breast cancer in the setting of distant metastatic disease has fallen dramatically over the past decade,1
but results from recent studies may alter this trend. Particularly with the more widespread use of effective systemic therapy, the potential to bring patients to the point of “no evidence of disease” via resection of the primary tumor is greater now than ever before.
Further, several authors have hypothesized that resection of the primary tumor may eliminate tumor stem cells and remove a source of tumor-induced immunosuppression, such that resection of the primary tumor may not only reduce tumor burden locally but also help in the clearance of systemic disease.
Although a number of retrospective studies have found that resection of the primary tumor in such patients is associated with improved survival, this is not uniformly the case. Nonetheless, a recent meta-analysis found that surgical resection of the primary tumor was associated with a hazard ratio (HR) for death of 0.63 (95% CI, 0.58-0.70).2
It is unclear, however, whether this improvement in overall survival (OS) represents the true effect of debulking or is simply reflective of the inherent selection bias favoring healthier patients with a lower tumor burden as surgical candidates.
Conflicting Data in Trials
Randomized controlled trials to elucidate the true impact of surgery in the setting of metastatic disease have produced seemingly conflicting results. Badwe et al reported the findings of an Indian trial (NCT00193778) in which 350 patients with metastatic disease were treated with systemic therapy and subsequently randomized to receive surgery or not.3
In this study, there was no significant difference in OS at 2 years of follow-up between the 2 groups (41.9% vs 43.0%, respectively; HR, 1.04; 95% CI, 0.81-1.34; P
= .79). Although patients treated with surgery in this study tended to have a lower rate of locoregional recurrence, they had a higher rate of progression to distant metastases.
Soran et al, on the other hand, in their trial of 274 Turkish patients who presented with metastatic disease, randomized patients to surgical resection versus no resection prior to systemic therapy.4
Their results were similar to those of the Indian trial in terms of OS when patients were followed to 3 years (OS, 68% vs 51%; P
= .79), but with 5 years of follow-up, investigators found a significant improvement in OS associated with surgery (41.6% vs 24.4%; HR, 0.66; 95% CI, 0.49-0.88; P
There are a number of factors that may help to reconcile the disparate outcomes of these 2 studies. First of all, the Turkish study had a longer follow-up: At 3 years, its findings were similar to those of the Indian trial. Secondly, in the Turkish trial, patients had surgery first; in the Indian trial, patients were treated with systemic therapy first.
Given the results of the National Surgical Adjuvant Breast and Bowel Project B-18 trial in the nonmetastatic setting, which showed no difference in survival in patients treated with neoadjuvant therapy followed by surgery versus surgery followed by adjuvant therapy, it is difficult to surmise how this could account for the difference, particularly when the response to treatment may be an indicator of improvement in survival with surgical resection (a question being posed by the ongoing ECOG trial).