Select Gene Mutations Associated with Survival Outcomes in ER-positive ERBB2-negative Early-stage Invasive Breast Cancer: A Single-institutional Tissue Bank Study

Overview

Journal Cancer Med

Specialty Oncology

Date 2024 Jul 20

PMID 39031010

Authors

Victor C Kok

To-Yu Huang

Yi-Chiung Hsu

Yuan-Ching Chang

Po-Sheng Yang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

PIK3CA mutational status in tissue and plasma as a prognostic biomarker in HR+/HER2- breast cancer.

Teran E, Lozano R, Rodriguez C, Abad M, Figuero L, Munoz J Cancer Med. 2024; 13(17):e70101.

PMID: 39235099 PMC: 11375731. DOI: 10.1002/cam4.70101.

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