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Breast cancer subtypes and the risk of distant metastasis at initial diagnosis: a population-based study

Authors Xiao W, Zheng S, Yang A, Zhang X, Zou Y, Tang H, Xie X

Received 10 June 2018

Accepted for publication 23 August 2018

Published 5 November 2018 Volume 2018:10 Pages 5329—5338


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Beicheng Sun

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.
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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