The Value of Primary Tumor Resection among Different Treatment Methods in Stage IV Breast Cancer: Robust Evidence for Prognostic Benefit
Authors: Pan Yuancan , Chen Dong , Wang Yue , Peng Yu , Yao Wentao , Lu Taicheng , Yuan Zichun , Kong Weijia , Yang Zhengzheng , Li Haiming , Zhang Jingzhi , Zhang Yutong , Shi Enze , Zhang Ganlin , Ma Tingting , Wang Xiaomin 
Published: November 2023

Abstract
Background: Primary tumor resection (PTR) in stage IV breast cancer (BC) patients currently lacks robust evidence supporting a prognostic benefit, and the guidelines do not actively endorse this practice. The circumstances under which patients may benefit from this procedure remain uncertain.
Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program in the United States offers treatment data for stage IV breast cancer patients. We conducted a screening of patients diagnosed with metastatic breast cancer between 2010 and 2015. The primary outcomes focused on were overall survival (OS) and cancer-specific survival (CSS). We employed Kaplan-Meier method, Cox proportional hazard regression models, propensity score matching (PSM) to balance key confounding variables, and sequential landmark analyses to mitigate the impact of time-related factors on the results.
Results: This study included 11,359 patients with stage IV breast cancer (BC). Patients who received primary tumor resection (PTR) experienced improved overall survival (OS) and cancer-specific survival (CSS). For OS (median survival time), the comparisons were as follows: chemoradiotherapy plus PTR versus chemoradiotherapy, with survival times of 56 months versus 25 months (p < 0.001); radiotherapy plus PTR versus radiotherapy, with survival times of 51 months versus 27 months (p < 0.001); chemotherapy plus PTR versus chemotherapy, with survival times of 45 months versus 32 months (p < 0.001); and only PTR versus no treatment, with survival times of 35 months versus 22 months (p < 0.001). Multivariate adjustment analysis, propensity score matching (PSM), and sequential landmark analyses provided further validation of these results. When stratified by different metastasis patterns, PTR significantly improved OS and CSS in patients with metastases in other organs, excluding brain metastasis. Regarding OS, the adjust hazard ratios (aHR) for different metastasis sites were as follows: bone metastasis (aHR0.555, 95% CI 0.514-0.598, p < 0.001); liver metastasis (aHR0.703, 95% CI 0.593-0.835, p < 0.001); brain metastasis (aHR0.639, 95% CI 0.549-0.734, p < 0.001); bone-liver metastasis (aHR0.716, 95% CI 0.601-0.852, p < 0.001); bone-lung metastasis (aHR0.782, 95% CI 0.667-0.915, p = 0.002); bone, liver, and lung metastasis (aHR0.712, 95% CI 0.550-0.921, p = 0.010). Notably, many patients with brain metastasis did not derive significant benefits from chemotherapy, and patients with liver metastasis saw improvements with radiotherapy alone. Similar conclusions were observed for cancer-specific survival (CSS).
Conclusion: In patients with stage IV breast cancer, PTR in combination with chemotherapy or chemoradiotherapy can improve survival time. However, in cases of solitary brain metastasis and multiple metastases including brain metastasis, the decision to use PTR should be made with caution.