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

Abstract

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; metastasis behavior; metastatic sites; molecular subtypes; prognosis.

Figure 1

Patient selection flow chart.

Figure 2

Distribution (percentage) of molecular subtypes in all breast cancer patients, and in patients with bone, lung, liver, and brain metastases (A); distribution (percentage) of molecular subtypes in all breast cancer patients and in patients with oligo-organ metastases (B). Abbreviations: met, metastasis; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; +, denotes positive; −, denotes negative.

Figure 3

Median survival time (months) of different distant metastatic diseases stratified by molecular subtypes. Abbreviations: HER2, human epidermal growth factor receptor 2; HR, hormone receptor; +, denotes positive; −, denotes negative.

Figure 4

Kaplan–Meier survival curves and log-rank test results of different molecular subtypes in the brain (A), liver (B), lung (C), and bone (D) metastases. Abbreviations: HER2, human epidermal growth factor receptor 2; HR, hormone receptor; +, denotes positive; −, denotes negative.