Metastatic breast cancer: Is systemic therapy the only effective treatment?

Dear Editor:

Breast cancer constitutes the most common worldwide cancer in women. There were more than 560,000 deaths from breast cancer worldwide in 2015 with a projected death rate predicted to rise to more than 800,000 deaths per year by 2030.¹ Systemic therapy is the first treatment for metastatic breast cancer (MBC). Although systemic therapy is broadly accepted as the first treatment for women with advanced breast cancer, several cohort prospective and retrospective studies have demonstrated an improved short-term overall survival with locoregional therapy, such as surgery. Wang et al. reported an increase in the 3-year overall survival (OS) for the surgery group compared to the non-surgery one (54.5% vs 47.7%) in a cohort retrospective study of 8142 patients with IV stage breast cancer.² Another retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) program demonstrated a longer 10-years overall survival for women who received surgery compared to those ones who did not receive it.³ Regardless the high amount of cohort studies on all possible alternative treatments to systemic therapy, there are not enough shared scientific studies demonstrating the superiority of locoregional therapy compared to systemic treatment in terms of overall survival and progression free-survival. Furthermore, it seems that improved survival changes according to the metastatic site (distant or local metastases), metastatic pattern (single or multiple organ metastases), characteristics of the IV stage breast cancer and patients’ performances status and age. One systematic review and meta-analysis conducted by Tosello et al.⁴ demonstrated that breast surgery plus systematic therapy improved local progression free-survival compared to systemic treatment alone, although overall survival and distant progression free-survival were not better in the first group of patients. Not only does surgery constitute the only locoregional possible treatment for patients with advanced breast cancer, but also radiotherapy represents an additional effective and safe local treatment for patients with local and distant metastases from breast cancer. The patients amenable to local treatment are those with oligometastasis, whose term refers to a low-volume metastatic disease with limited number and size of lesions (up to five and not necessarily in the same organ). Unfortunately, nowadays there is not enough data to select the best local technique for individual patients with oligometastatic involvement, such as surgery, radiofrequency ablation. The only recent ongoing randomized prospective study on the local management of metastatic breast cancer is the ECOG-E2108 trial with 391 women with stage IV breast cancer, presented at the 2020 ASCO Annual Meeting in the Plenary session. In the absence of enough data from the literature, all therapeutic strategies concerning the removal of primary tumors or local and distant metastases could be an attractive approach to MBC patients. Thus, prospective randomized trials are required to create worldwide guidelines on the treatment of advanced breast cancer, comprising well-described locoregional treatment, and a vast global collaboration on MBC should be instituted to confirm its impact on short and long-term survival and ensure optimal statistical strength of the results.