Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Low and Ultra-low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes

Mariausilia Franchina
ORCID logo ,
Cristina Pizzimenti
,
Vincenzo Fiorentino
,
Maurizio Martini
ORCID logo ,
Giuseppina Rosaria Rita Ricciardi
,
Nicola Silvestris
,
Antonio Ieni
ORCID logo ,
Giovanni Tuccari
* ORCID logo
Version 1 : Received: 22 June 2023 / Approved: 23 June 2023 / Online: 23 June 2023 (11:55:10 CEST)

A peer-reviewed article of this Preprint also exists.

Franchina, M.; Pizzimenti, C.; Fiorentino, V.; Martini, M.; Ricciardi, G.R.R.; Silvestris, N.; Ieni, A.; Tuccari, G. Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes. International Journal of Molecular Sciences 2023, 24, 12795, doi:10.3390/ijms241612795. Franchina, M.; Pizzimenti, C.; Fiorentino, V.; Martini, M.; Ricciardi, G.R.R.; Silvestris, N.; Ieni, A.; Tuccari, G. Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes. International Journal of Molecular Sciences 2023, 24, 12795, doi:10.3390/ijms241612795.

Abstract

HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, re-considering the immunohistochemical negative score of 0, 1+ or score of 2+/in situ hybridization (ISH) negative phenotype. In the present review we have outlined the needed criteria to exactly distinguish HER2 low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating these group sof tumors. In particular, Trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC has been recently approved by the U.S. Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally we hope that new guidelines may help to codify HER2 low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.

Keywords

HER2 expression; Breast cancer; Neoadjuvant treatment; HER2-low carcinomas; HER2 ultra-low carcinomas

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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