Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer.

BACKGROUND

Approximately 80% of all breast cancers (BCs) are currently categorized as human epidermal growth factor receptor 2 (HER2)-negative [immunohistochemistry (IHC) 0, 1+, or 2+/in situ hybridization (ISH) negative]; approximately 60% of BCs traditionally categorized as HER2-negative express low levels of HER2. HER2-low (IHC 1+ or IHC 2+/ISH-) status became clinically actionable with approval of trastuzumab deruxtecan to treat unresectable/metastatic HER2-low BC. Greater understanding of patients with HER2-low disease is urgently needed.

PATIENTS AND METHODS

This global, multicenter, retrospective study (NCT04807595) included tissue samples from patients with confirmed HER2-negative unresectable/metastatic BC [any hormone receptor (HR) status] diagnosed from 2014 to 2017. Pathologists rescored HER2 IHC-stained slides as HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 IHC 0 after training on low-end expression scoring using Ventana 4B5 and other assays at local laboratories (13 sites; 10 countries) blinded to historical scores. HER2-low prevalence and concordance between historical scores and rescores were assessed. Demographics, clinicopathological characteristics, treatments, and outcomes were examined.

RESULTS

In rescored samples from 789 patients with HER2-negative unresectable/metastatic BC, the overall HER2-low prevalence was 67.2% (HR positive, 71.1%; HR negative, 52.8%). Concordance was moderate between historical and rescored HER2 statuses (81.3%; κ = 0.583); positive agreement was numerically higher for HER2-low (87.5%) than HER2 IHC 0 (69.9%). More than 30% of historical IHC 0 cases were rescored as HER2-low overall (all assays) and using Ventana 4B5. There were no notable differences between HER2-low and HER2 IHC 0 in patient characteristics, treatments received, or clinical outcomes.

CONCLUSIONS

Approximately two-thirds of patients with historically HER2-negative unresectable/metastatic BC may benefit from HER2-low-directed treatments. Our data suggest that HER2 reassessment in patients with historical IHC 0 scores may be considered to help optimize selection of patients for treatment. Further, accurate identification of patients with HER2-low BC may be achieved with standardized pathologist training.

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure All authors received nonfinancial support (assistance with manuscript preparation) from Articulate Science, LLC, and Helios Medical Communications Ltd funded by AstraZeneca. Additional disclosures are as follows: GV reports consulting or advisory fees from Agilent, AstraZeneca, Daiichi Sankyo, and Roche; participation in speakers bureaus and data safety monitoring advisory boards for Agilent, AstraZeneca, Daiichi Sankyo and MSD Oncology, and Roche; personal travel fees from AstraZeneca and Roche; and grants from Roche. MB reports consulting or advisory fees from AstraZeneca and Roche Canada; and contracted research funding from Pfizer Canada. NN reports grants from Chugai, Daiichi Sankyo, Eisai, Lilly, Mochida, Novartis, and Pfizer; and participation in speakers bureaus for AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Lilly, Novartis, and Pfizer. ET reports consulting or advisory fees from Daiichi Sankyo and Lilly; and fees for non-CME services from AstraZeneca, Daiichi Sankyo, and Lilly. SB reports consulting or advisory fees from AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi; and contracted research funding from AstraZeneca, Lilly, GSK, MSD, Novartis, Pfizer, and Roche. FPL reports consulting or advisory fees from Agendia, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, GSK, MammaPrint, MSD, Myriad Genetics, Novartis, Pfizer, Roche, Seagen, and Veracyte; contracted research funding from AstraZeneca, MammaPrint, MSD, Myriad Genetics, Roche, and Veracyte; and personal travel fees from AstraZeneca and Seagen. NH reports participation in speakers bureaus for AstraZeneca, Chugai, Genomic Health, Kirin, Novartis, and Pfizer. JS reports research funding from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi; and partnerships with Roche. RTS reports consulting and non-CME service fees from AstraZeneca, Gilead, Lilly, Novartis, and Pfizer. AMB reports consulting or advisory fees from AbbVie, Agendia, Bayer, Biotheranostics, Coherus BioSciences, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, General Electric, Gilead Sciences, Immunomedics, Merck, Michael J. Hennessy Associates, Myriad Genetics, Novartis, OncLive, Pfizer, Puma Biotechnology, Seagen, and Tyme; and contracted research funding from AstraZeneca, Daiichi Sankyo, Lilly, Genentech/Roche, Gilead Sciences, Merck, Novartis, and Puma Biotechnology. CSO reports consulting or advisory fees from Roche and Seagen; and participation in speakers bureaus for Lilly. FS reports no conflict of interests. GH reports being a shareholder in Rhythm Biosciences Limited. DV reports a consulting or advisory role with OPEN Health; employment with AstraZeneca and may own stock or stock options in that company. GDJ reports a consulting or advisory role with AstraZeneca/MedImmune. AM is an employee of Daiichi Sankyo and may own stock or stock options in that company. AL and VGM are employees of AstraZeneca and may own stock or stock options in that company. Data sharing Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Data for studies directly listed on Vivli can be requested through Vivli at www.vivli.org. Data for studies not listed on Vivli could be requested through Vivli at https://vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli-platform/. AstraZeneca Vivli member page is also available outlining further details: https://vivli.org/ourmember/astrazeneca/. Disclaimers Medical writing support was funded by AstraZeneca in accordance with Good Publication Practice (GPP) guidelines (http://www.ismpp.org/gpp-2022). The manuscript was reviewed for medical accuracy by AstraZeneca and Daiichi Sankyo; however, the authors retained full control of the content and made the final decisions for all aspects of this article.