Abstract S2-02: Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: A randomized controlled trial

Abstract BACKGROUND: The role of loco-regional treatment, in women with metastatic breast cancer (MBC) at first presentation, is debatable. Preclinical evidence suggests that such treatment may facilitate growth of metastatic disease. On the other hand, many retrospective analyses in clinical cohorts have suggested favorable impact of loco-regional treatment in these patients. However, these results are likely to be influenced by selection bias. We conducted a prospective randomized controlled trial to assess the impact of loco-regional treatment on outcome in women with metastatic breast cancer at initial diagnosis. [NCT00193778] METHODS: Women with metastatic breast cancer at initial diagnosis and planned to be treated with anthracycline based chemotherapy (CT) were registered for the study. Those who had objective tumor response after 6 cycles of CT were randomized to one of the following arms: ‘LRT’ (loco-regional treatment) or ‘No-LRT’ (no loco-regional treatment). Patients were stratified by endocrine receptor (ER) status, site of metastases (visceral Vs bone Vs both) and number of metastatic lesions (< 3 Vs > 3). Women in LRT arm received surgery (breast conservation or mastectomy plus axillary lymph node dissection) followed by radiation therapy (RT), as per standard adjuvant guidelines. Women in No-LRT arm were followed up without surgery and RT. Both groups received standard endocrine therapy after last cycle of chemotherapy, if indicated. They were regularly followed up with clinical evaluation. Appropriate imaging was performed within 6 months after randomization and thereafter as clinically indicated. The primary endpoint was overall survival (OS). RESULTS: Between Feb 2005 and Jan 2013, 350 women were randomized, 173 in LRT and 177 in No-LRT arm. The data cutoff was in May 2013. The two arms were balanced with respect to age, clinical tumor size, HER2 receptor status and stratification factors. Eight (5.8%) patients in the LRT arm did not undergo loco-regional therapy while 19 (10.7%) patients in the No-LRT arm underwent surgical removal of primary tumor because of palliative reasons. The median follow-up was 17 months and 218 deaths (LRT = 111/173, No-LRT = 107/177) had been recorded at data cutoff. The median OS in LRT and No-LRT arms were 18.8 and 20.5 months (HR = 1.07, 95%CI = 0.82-1.40, p = 0.60) and the corresponding 2-year OS were 40.8% and 43.3%, respectively. After adjusting for age, ER status, HER2 receptor status, site of metastases and number of metastatic lesions in a Cox regression model, there was no significant difference in OS between LRT and No-LRT arms (HR = 1.00, 95%CI = 0.76-1.33, p = 0.98). There was no interaction between the effect of LRT and covariates in the model. CONCLUSIONS: Loco-regional treatment of the primary tumor and axillary nodes has no impact on OS in patients diagnosed with MBC at initial presentation, who have responded to frontline chemotherapy. We were unable to identify any subgroups that are likely to benefit from LRT. Such treatment should be reserved for women who need it for palliative reasons. Detailed analysis will be presented at the Symposium. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S2-02.