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

HER2-Low Breast Cancer: Where Are We?

Chiara Molinelli  1   2 , Flavia Jacobs  1   3   4 , Caterina Marchiò  5   6 , Francesca Pitto  7 , Maurizio Cosso  8 , Stefano Spinaci  9 , Evandro de Azambuja  1 , Francesco Schettini  10   11 , Elisa Agostinetto  1 , Matteo Lambertini  2   12
Affiliations
Review

HER2-Low Breast Cancer: Where Are We?

Chiara Molinelli et al. Breast Care (Basel). 2022 Dec.

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.

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Conflict of interest statement

Dr. Molinelli received honoraria from Novartis and Lilly outside the submitted work. Dr. Jacobs declares no conflicts of interest. Dr. Agostinetto received consultancy fees or honoraria from Eli Lilly and Sandoz and support to attend medical conferences from Roche, Novartis, Eli Lilly, and Genetic, Istituto Gentili (all disclosures are outside the submitted work). Dr. Marchiò received honoraria from Bayer, Roche, AstraZeneca, and Daiichi Sankyo. Dr. De Azambuja received honoraria and/or participated to advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbs, and Pierre Fabre; received travel grants from Roche/GNE and GSK/Novartis; and received research grant to his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier. Dr. Schettini received personal fees from Novartis for educational material. Dr. Lambertini played an advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences and received speaker honoraria from Roche, Daiichi Sankyo, Lilly, Novartis, Pfizer, Sandoz, Libbs, and Takeda and travel grants from Gilead outside the submitted work.

Figures

Fig. 1
Fig. 1
a Hormone receptor status distribution within HER2-low breast cancer. Original figure based on data available in the literature [7, 8, 11, 12, 13, 14]. b PAM50 intrinsic subtype distribution in HER2-low tumors. The figure illustrates the percentages of PAM50 intrinsic subtype within HR+/HER2-low and HR−/HER2-low subgroups (i.e., for HR+/HER2-low: luminal A 58.9–65.9%, luminal B 25.4–33.4%, HER2-enriched 1.2–3.0%, basal-like 1.9–3.6%, normal-like 2.8–3.9%. For HR−/HER2-low: luminal A 1.4–1.6%, luminal B 0%, HER2-enriched 7.1–13.7%, basal-like 76.7–83.3%, normal-like 7.9–8.2%). Original figure based on data available in the literature [7, 12]. HR, hormone receptor.
See this image and copyright information in PMC

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