Select gene mutations associated with survival outcomes in ER‐positive ERBB2‐negative early‐stage invasive breast cancer: A single‐institutional tissue bank study

Introduction The prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor‐positive, human epidermal growth factor receptor‐2‐negative early‐stage invasive breast cancer (EBC) in a real‐world setting is uncertain. Therefore, we aimed to determine the correlation between a 22‐gene mutational profile and long‐term survival outcomes in patients with ER+/ERBB2‐ EBC. Patients and Methods A total of 73 women diagnosed with ER+/ERBB2‐ EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse‐free survival (RFS) and overall survival (OS). The log‐rank test derived p‐value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. Results At follow‐up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty‐three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85‐fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60–5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6‐fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31–18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32–27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes. Conclusions Our single‐institution tissue bank study of Taiwanese women with ER+/ERBB2‐ EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes. We studied the prognosis of a 22‐gene mutational profile using tissue bank tumors of 73 women with ER+/ERBB2‐ EBC. This cohort of female patients had extended follow‐up, reaching 18.8 years. Any mutation in the MAP2K4, FGFR3, APC, KIT, RB1, and PTEN genes would have a 5.8‐fold increased risk of relapse.