| Summary: | Weikai Xiao,1,* Shaoquan Zheng,1,* Anli Yang,2,* Xingcai Zhang,3,* Yutian Zou,1 Hailin Tang,1 Xiaoming Xie1 1Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Medicine; Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; 3Department of Applied Physics, Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02138, USA *These authors contributed equally to this work Background: It was unclear whether breast cancer subtypes are associated with the risk of site-specific metastases. This study aimed to evaluate the relationship between molecular subtypes and distant metastatic sites and their prognostic significance. Methods: We identified 295,213 patients with invasive breast cancer from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Subtypes were classified into four categories: hormone receptor (HR+)/human epidermal growth factor receptor 2 (HER2−), HR+/HER2+, HR−/HER2+, and triple-negative (HR−/HER2−). Logistic regression was used to assess the association between metastasis location and subtypes. Multivariate Cox models were used to estimate the overall survival (OS) of related factors. Results: According to our study, 3.28%, 1.52%, 1.20%, and 0.35% of newly diagnosed breast cancers presented bone, lung, liver, and brain metastases at diagnosis, respectively. Both metastatic sites and subtypes significantly affected the OS after metastasis. In multivariate analysis, HR+/HER2+ subtype (OR as compared with HR+/HER2− subtype, 1.30 [95% CI, 1.22–1.39]) significantly correlated with elevated bone metastasis risk, whereas HR−/HER2+ did not. Both HER2+ subtypes (HR+/HER2+ and HR−/HER2+) were significantly associated with higher rates of liver, brain, and lung metastases, while the highest OR was observed in liver metastases. Triple-negative tumors had a higher rate of brain (OR, 1.95 [95% CI, 1.61–2.35]), liver (OR, 1.35 [95% CI, 1.20–1.51]), and lung metastases (OR, 1.34 [95% CI, 1.21–1.47]), but a significantly lower rate of bone metastases (OR, 0.64 [95% CI, 0.59–0.69]) than HR+/HER2− tumors. Conclusions: Breast cancer subtypes are associated with different metastatic patterns and confer different prognostic impacts. Molecular subtypes can identify patients at increased risk of site-specific metastases. Keywords: breast cancer, molecular subtypes, metastasis behavior, prognosis, metastatic sites
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