Impact of molecular subtypes on metastatic behavior and overall survival in patients with metastatic breast cancer: A single-center study combined with a large cohort study based on the Surveillance, Epidemiology and End Results database

Abstract

Breast cancer is a highly heterogeneous disease at the molecular level and >90% of mortalities are due to metastasis and its associated complications. The present study determined the impact of molecular subtypes on metastatic behavior and overall survival (OS) of patients with metastatic breast cancer. The influence of molecular subtypes on the sites and number of metastases in 166 patients with metastatic breast cancer from a single center were assessed; and the influence of molecular subtypes on the sites and number of metastases and OS in 15,322 metastatic cases among 329,770 patients with primary breast cancer from the Surveillance, Epidemiology and End Results database were assessed. Analysis of both datasets revealed that different molecular subtypes exhibited differences in the prevalence of different metastatic sites and number of metastases. A larger proportion of bone metastasis was observed in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ subtype than in other subtypes, more lung metastasis was observed in the HR-/HER2+ subtype and more liver metastasis occurred in the HR+/HER2+ and HR-/HER2+ subtypes. Single-site metastasis was more common for the HR+/HER2- subtype than in other subtypes, while 2-3 sites of metastases were more common for the HR+/HER2+ subtype and ≥4 sites of metastases were more frequent in the HR-/HER2+ and HR-/HER2- subtypes. The mean OS of patients with primary breast cancer in the HR+/HER2- subtype group was the longest (78.5 months), while the HR-/HER2- group had the shortest mean OS (69.1 months). The mean OS of the metastatic HR+/HER2+ group was the longest (46.0 months), while the mean OS of the metastatic HR-/HER2- group was the shortest (18.5 months). In conclusion, the results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS.

Keywords: breast cancer; metastatic sites; molecular subtypes; number of metastatic sites; overall survival.

Figure 1.

Flowchart of patient inclusion in the present cohort study based on the SEER database. SEER, Surveillance, Epidemiology and End Results; HR, hormone receptor; HER2, human epidermal growth factor receptor 2; DLN, distant lymph node.

Figure 2.

Frequencies of metastasis locations in 166 patients with metastatic breast cancer of the present cohort study according to molecular subtype. Frequencies of different metastatic sites in patients with breast cancer with involvement of (A) one, (B) two, (C) three and (D) four metastatic sites by each breast cancer subtype. DLN, distant lymph node; HR, hormone receptor; HER2, human epidermal growth factor receptor 2.

Figure 3.

Frequencies of metastasis locations in patients with metastatic breast cancer from the Surveillance, Epidemiology and End Results dataset (n=15,322) according to molecular subtype. Frequencies of different metastatic sites in patients with breast cancer with involvement of (A) one, (B) two, (C) three and (D) four metastatic sites by each breast cancer subtype. DLN, distant lymph node; HR, hormone receptor; HER2, human epidermal growth factor receptor 2.

Figure 4.

Influence of molecular subtypes on the OS of patients with primary breast cancer and with metastatic breast cancer based on the SEER database. (A) OS of 329,770 patients with primary breast cancer by molecular subtype; Log-rank P<0.001. (B) OS of 15,322 patients with metastatic breast cancer by molecular subtype; Log-rank P<0.001. OS, overall survival; SEER, Surveillance, Epidemiology and End Results; HR, hormone receptor; HER2, human epidermal growth factor receptor 2; Cum, cumulative survival. The definition of any censored datapoints: alive that their total time until death could not be determined; or dead of other cause; or missing.