HER2-Low Breast Cancer: Where Are We?

Chiara Molinelli; Flavia Jacobs; Caterina Marchiò; Francesca Pitto; Maurizio Cosso; Stefano Spinaci; Evandro de Azambuja; Francesco Schettini; Elisa Agostinetto; Matteo Lambertini

doi:10.1159/000527391

HER2-Low Breast Cancer: Where Are We?

Breast Care (Basel). 2022 Dec;17(6):533-545. doi: 10.1159/000527391. Epub 2022 Oct 6.

Authors

Chiara Molinelli^{1

2}, Flavia Jacobs^{1

3

4}, Caterina Marchiò^{5

6}, Francesca Pitto⁷, Maurizio Cosso⁸, Stefano Spinaci⁹, Evandro de Azambuja¹, Francesco Schettini^{10

11}, Elisa Agostinetto¹, Matteo Lambertini^{2

12}

Affiliations

¹ Academic Trials Promoting Team, Institut Jules Bordet, L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium.
² Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa, Italy.
³ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
⁴ IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Rozzano, Milan, Italy.
⁵ Department of Medical Sciences, University of Turin, Turin, Italy.
⁶ Pathology Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.
⁷ Department of Pathology, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁸ Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁹ Department of Surgery, Ospedale Villa Scassi, Genova, Italy.
¹⁰ Medical Oncology Department, Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain.
¹¹ Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
¹² Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Abstract

Background: Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called "HER2-low" category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies.

Summary: The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs.

Key message: Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field.

Keywords: Breast cancer; HER2-low; Trastuzumab deruxtecan.

Publication types

Review

Grants and funding

Matteo Lambertini acknowledges the support by the Italian Association for Cancer Research (“Associazione Italiana per la Ricerca sul Cancro”, AIRC; MFAG 2020 ID 24698), the Italian Ministry of Health (5×1000 funds 2017), and the IRCCS Ospedale Policlinico San Martino (“Ricerca Corrente” funds). Francesco Schettini is the recipient of a 2020 European Society for Medical Oncology (ESMO) Fellowship − Translational and of the 2021 BBVA Foundation/Hospital Clinic of Barcelona Joan Rodés − Jose Baselga Advanced Research Contract in Oncology. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the author(s) and do not necessarily reflect those of funding entities.