Reassessing Estrogen Receptor Expression Thresholds for Breast Cancer Prognosis in HER2-Negative Patients Using Shape Restricted Modeling

Authors

Wenli Dong
Takeo Fujii
Jing Ning
Toshiaki Iwase
Jing Qin
Naoto T Ueno
Yu Shen

Publication Date

2-15-2025

Journal

Scientific Reports

Abstract

We used a novel shape-restricted Cox model to determine the desirable ER expression cutoff to predict breast cancer prognoses. Our model treats ER as a continuous variable using a flexible monotone-shaped Cox regression to assess its association with survival outcomes holistically. The study included 3055 patients with stage II/III HER2-negative breast cancer. The primary outcomes were time to recurrence or death (TTR) and overall survival (OS). The shape-restricted Cox model identified 10% ER as the preferred cutoff to predict TTR. The finding was confirmed by the log-rank test and standard Cox model that patients with ER ≥ 10% had TTR benefit over ER <  10% (log-rank p <  0.001). No OS or TTR benefit of adjuvant endocrine therapy was observed in patients with 1% ≤ ER <  10% (HR 0.877, 95% CI 0.481-1.600, p = 0.668 for TTR and HR 0.698, 95% CI 0.337-1.446, p = 0.333 for OS). Using the shape-restricted Cox model, this study suggests a potential preferred threshold of 10% for predicting TTR. The findings could assist physicians in effectively weighing the benefits and risks of adjuvant endocrine therapy for patients with ER <  10% disease, particularly in cases involving severe adverse events.

Keywords

Humans, Female, Breast Neoplasms, Receptors, Estrogen, Receptor, ErbB-2, Prognosis, Middle Aged, Proportional Hazards Models, Adult, Aged, Biomarkers, Tumor, Endocrine therapy, Estrogen receptor, Modelling, Survival, Threshold

DOI

10.1038/s41598-025-90134-9

PMID

39955419

PMCID

PMC11829975

PubMedCentral® Posted Date

2-15-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes