Poor prognosis of male triple-positive breast Cancer patients: a propensity score matched SEER analysis and molecular portraits

Abstract

The purpose of this study was to explore clinicalpathology features, molecular features and outcome of male breast cancer patients who expressed ER, PR as well as HER-2, namely triple-positive male breast cancer (TP-MBC), and compared them with triple-positive female breast cancer patients (TP-FBC). TP-MBC and TP-FBC from 2010 to 2017 were selected from the Surveillance, Epidemiology, and End Results database (SEER). Kaplan-Meier plotter and multivariable Cox regression model were applied to analyse the difference between TP-MBC and TP-FBC on cancer-specific survival (CSS) and overall survival (OS). Propensity score matched (PSM) analysis was used to ensure well-balanced characteristics. 7 cases TP-MBC and 174 cases TP-FBC patients with the genomic and clinical information were identified from the cohort of The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering (MSK). 336 TP-MBC and 33,339 TP-FBC patients were taken into the study. The percentages of TP-MBC in MBC patients were higher than the rates of TP-FBC in FBC patients from 2010 to 2017 except 2012. Compared with TP-FBC, more TP-MBC were staged III (17.9% vs. 13.5%) or stage IV (11.0% vs. 6.9%). TP-MBC were more frequently to be older than 65-years-old (47.0% vs. 29.3%), Balck (15.2% vs. 10.8%), ductal carcinoma (91.7% vs. 84.4%) and metastases to lung (4.5% vs. 2.1%) or bone (8.6% vs. 4.7%). TP-MBC had worse OS and CSS than TP-FBC in all stages (P < 0.001). In multivariable prediction model of TPBC, male patients had a higher risk than female. Lastly, the worse OS (P < 0.001) and CSS (P = 0.013) were seen in the 1:3 PSM analysis between TP-MBC and TP-FBC. Genomic analysis revealed that TP-MBCs have some notable rare mutations, like ERBB2, ERBB3, RB1, CDK12, FGFR2, IDH1, AGO2, GATA3, and some of them are not discovered in TP-FBC. TP-MBC had a worse survival than TP-FBC, and there were different genomic features between two groups. Current knowledge and treatment to TP-MBC maybe inadequate and remain to be explored.