Primary-Site Local Therapy for Patients with De Novo Metastatic Breast Cancer: An Educational Review

Background: Until 2001, the paradigm guiding the management of women with de novo metastatic breast cancer (dnMBC) stipulated that primary-site locoregional therapy (PSLT) did not alter the course of metastatic disease and was necessary only for palliation of symptoms. Since 2002, retrospective data have begun questioning this paradigm. However, selection biases driving an observed survival advantage associated with PSLT in dnMBC were quickly recognized and led to several randomized clinical trials (RCTs) addressing this question. Methods and Results: Four published RCTs have since tested the value of PSLT added to systemic therapy (ST) or not, with overall survival (OS) as the primary end point. The results of three published trials show no OS benefit for the addition of PSLT: Indian Tata Memorial, U.S./Canada E2108, and Austrian POSYTIVE (although POSYTIVE did not reach full accrual). The fourth RCT (Turkey, MF07-01) shows an OS benefit for PSLT at 5 years (42 % vs 24 % in the ST arm; hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.49–0.88). However, the 5-year survival in the PSLT arm of MF07-01 is similar to that in both arms of E2108, suggesting that the worse survival in the ST arm of MF07-01 is a result of biologically worse disease (from imbalanced randomization). Locoregional control was improved by PSLT in all trials, but without improvement in quality of life. Conclusions: The current evidence fails to refute the 20th century paradigm guiding management of de novo metastatic breast cancer. Discussion continues regarding the survival value of PSLT for patients with bone-only disease or oligometastases, but unbiased evidence is lacking.