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

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.

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.

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.