The Uncharted Role of HER2 Mutant Alleles in Breast Cancer

Authors

Rashi Kalra
Bora Lim
Matthew J Ellis
Shyam M Kavuri

Publication Date

10-31-2023

Journal

Oncotarget

Abstract

Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.

Keywords

Humans, Female, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Alleles, Receptor, ErbB-2, metastasis, poziotinib, HER2, neratinib, invasive lobular breast carcinoma

DOI

10.18632/oncotarget.28489

PMID

37921670

PMCID

PMC10624202

PubMedCentral® Posted Date

October 2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes