Prevalence of HER2-Low Status and Outcomes in Early-Stage HER2-Negative Breast Cancer

Authors

Akshara Singareeka Raghavendra
Diane D Liu
Sarah Pasyar
Senthil Damodaran
Yu Shen
Jason A Mouabbi
Carlos H Barcenas
Debu Tripathy

Language

English

Publication Date

2-9-2026

Journal

npj Breast Cancer

DOI

10.1038/s41523-026-00901-8

PMID

41663430

PMCID

PMC12996595

PubMedCentral® Posted Date

2-9-2026

PubMedCentral® Full Text Version

Post-print

Abstract

HER2-low breast cancer (IHC 1+ or 2+ without HER2 gene amplification) is a distinct and understudied subtype. In a cohort of 14,593 early-stage breast cancer patients treated at MD Anderson from 2006 to 2019, 60.4% were HER2-low. Multivariable analysis showed HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and estrogen receptor (ER) positivity. Among 2464 patients receiving neoadjuvant chemotherapy, HER2-low status was not linked to pathologic complete response (pCR), overall survival (OS), or disease-free survival (DFS) compared to HER2-0 tumors. Factors predicting pCR included nuclear grade III, stage I, invasive ductal carcinoma, lower ER/PR expression, and absence of lymphovascular invasion (LVI). Patients with TNBC had significantly higher pCR rates (31.9%) than those with luminal type (2.2%, p <  0.0001). Longer OS and DFS were associated with non-White race, lower stage and grade, negative LVI, and higher ER/PR levels. These findings confirm HER2-low status is common but not independently prognostic for response or survival.

Keywords

Cancer, Oncology

Published Open-Access

yes

Recommended Citation

Singareeka Raghavendra, Akshara; Liu, Diane D; Pasyar, Sarah; et al., "Prevalence of HER2-Low Status and Outcomes in Early-Stage HER2-Negative Breast Cancer" (2026). Faculty, Staff and Student Publications. 6514.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6514