The association between molecular type and prognosis of patients with stage IV breast cancer: an observational study...

Molecular subtype, the basis for personalized treatment of breast cancer, is of great value in evaluating prognosis and guiding treatment of early-stage breast cancer. However, its value in stage IV patients remains unclear. In this study, we investigated the association between molecular subtype and prognosis of de novo stage IV breast cancer using Surveillance, Epidemiology, and End Results (SEER) database with the purpose to provide evidence for optimal therapeutic options for breast cancer patients.

We retrospectively analyzed de novo stage IV breast cancer patients with the SEER Program data from 2010 to 2015. Characteristics of patients with different molecular subtypes were compared by chi-square test and survival curves for breast cancer specific survival (BCSS) according to subtypes were plotted by Kaplan-Meier method. The Cox proportional hazards model was performed to search for independent prognostic factors in stage IV breast cancer patients.

A total of 11,974 patients were included in this study, among which 7,100 (59.30%) patients were of HR⁺/HER2^-, 2,093 (17.48%) of HR⁺/HER2⁺, 1,139 (9.51%) of HR^-/HER2⁺ and 1,642 (13.71%) of HR^-/HER2^-. Multivariate Cox analysis revealed that molecular subtype, age, race, marital status, grade, surgery and chemotherapy were independent prognostic factors for BCSS in de novo stage IV patients. Taking HR⁺/HER2^- patients as reference, HR⁺/HER2⁺ patients had better BCSS (HR =0.81, 95% CI: 0.75-0.88, P<0.001), HR^-/ HER2^- patients had worse BCSS (HR =1.42, 95% CI: 1.29-1.46, P<0.001) and HR^-/HER2⁺ patients had no significant difference (HR =1.03, 95% CI: 0.98-1.08, P=0.188). In patients with different single organ metastases, the prognosis of HR⁺/HER2⁺ subtype was the best (except brain metastasis), while that of HR^-/HER2^- subtype was the worst.

Molecular subtypes were closely associated with the prognosis of de novo stage IV breast cancer. Among the four subtypes, HR⁺/HER2⁺ patients had the best prognosis while HR^-/HER2^- patients had the worst. The prognosis of patients with different single organ metastases was the same, but in patients with brain metastases, HR⁺/HER2⁺ ones did not have a significantly better prognosis than other subtypes except triple-negative type.