Reconsidering the Definition of Triple-Negative Breast Cancer in the Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value for Hormone Receptor Percentage of HER2-Negative Invasive Breast Cancer

Authors

Takeo Fujii
Toshiaki Iwase
Yu Shen
Jami Fukui
Naoto T Ueno

Language

English

Publication Date

1-1-2026

Journal

British Journal of Cancer

DOI

10.1038/s41416-025-03197-w

PMID

41109918

PMCID

PMC12555794

PubMedCentral® Posted Date

10-28-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

The optimal cut-off values of estrogen receptor (ER) and progesterone receptor (PgR) expression to define the positivity of ER and PgR have been under discussion for over a decade but remain controversial. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the St. Gallen International Expert Consensus recommended that breast cancers with ≥1% of ER or PgR expression should be considered hormone receptor (HR)-positive tumors but ER/PR expression of 1% to 10% should be reported as HR-low positive; however, among HER2-negative disease, data on the overall benefit of adjuvant endocrine therapies for patients with HR-low positive disease is limited, resulting in the revisiting of the definition of triple-negative breast cancer (TNBC). Defining HR-low positive disease by better understanding the biology is essential because of the recent advancement of neoadjuvant and adjuvant systemic therapy strategies, including immune checkpoint inhibitors (ICIs) for TNBC. Additionally, identifying who should be treated with adjuvant endocrine therapy, particularly those who have HR-low HER2-negative disease, which is currently treated as TNBC without adjuvant endocrine therapy, is a clinical unmet need. In clinical practice, treating physicians have tailored systemic treatment strategies using other clinical and pathological factors (i.e., age, grade, Ki-67, tumor size, lymph node involvement). There is no universal practice to treat patients with HR-low HER2-negative breast cancer. This review summarized the currently available data to define the clinically relevant optimal cut-off values of ER/PgR in neoadjuvant- and adjuvant-setting. We recommend considering creating a novel category of triple-negative like breast cancer (TN-like BC), which will require a therapeutic strategy different from conventional TNBC.

Keywords

Humans, Triple Negative Breast Neoplasms, Female, Erb-b2 Receptor Tyrosine Kinases, Receptors, Progesterone, Receptors, Estrogen, Immune Checkpoint Inhibitors, Biomarkers, Tumor

Published Open-Access

yes

Recommended Citation

Fujii, Takeo; Iwase, Toshiaki; Shen, Yu; et al., "Reconsidering the Definition of Triple-Negative Breast Cancer in the Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value for Hormone Receptor Percentage of HER2-Negative Invasive Breast Cancer" (2026). Faculty, Staff and Student Publications. 6512.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6512