The potential markers of endocrine resistance among HR+ /HER2+ breast cancer patients

Purpose: Breast cancer with positive hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) is a special subgroup with different clinical features and survival, especially the endocrine therapy resistance. The main purpose of the study is to find the potential markers to predict the survival and endocrine therapy resistance of patients with HR+ /HER2+ breast cancer. Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to collect patients’ clinical information and tumor features including age, tumor size, grade, stage and long-term survival; the BioPortal for Cancer Genomics (https://cbioportal.org) was used to download the gene data for specific patient group; cluster analyses of gene expression were conducted through the DAVID Bioinformatics Resources 6.8 software. Results: All of the included patients were diagnosed as HR positive breast cancer, but the PR positive rates were more common in HER2- group and also the ER+ /PR+ disease. Patients in HR+ /HER2+ group were more likely to present as stage III–IV and grade III disease. Among HR+ /HER2+ patients, 68.6% received chemotherapy, while only 28.9% in HR+ /HER2– group received chemotherapy (P < 0.0001). The survival of HR+ /HER2+ group was poorer. From TCGA database, series genes which were differed between HR+ /HER2+ and HR+ /HER2– were screened out that related to ERBB2 closely: IKZF3, LASP1, CDK12, MLLT6, and RARA. The first three candidate genes were associated with patients’ survival, especially in patients who received hormone therapies. Conclusion: This study analyzed the clinical characteristics and survival of patients with HR+/HER2+ breast cancer as a special subgroup. ERBB2, IKZF3, LASP1, and CDK12 were the potential markers of the resistance of endocrine therapy, and they will provide new strategies for clinicians.