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