Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer

Moutafi, Myrto; Robbins, Charles J.; Yaghoobi, Vesal; Fernandez, Aileen I.; Martinez-Morilla, Sandra; Xirou, Vasiliki; Bai, Yalai; Song, Yee Jiun; Gaule, Patricia; Krueger, Joseph S.; Bloom, Kenneth J.; Hill, Salisha; Liebler, D.C.; Fulton, Regan; Rimm, David L.

doi:10.1038/s41374-022-00804-9

Cited by 71 publications

(56 citation statements)

References 32 publications

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“…In parallel with existing techniques, novel methods to quantify HER2 levels or standardize procedures are being investigated, including quantitative assays to measure HER2 protein expression at the single cell level, automated scoring of HER2 FISH, microRNA signatures in primary tumour tissue as a prognostic/ predictive tool, using a mass spectrometry system to measure HER2 at attomols mm 2 (refs. [270][271][272][273] ). Furthermore, gene expressionbased tools for prognostic and predictive purposes are also under evaluation in HER2 + breast cancer, although none of these has yet reached mainstream use 274,275 .…”

Section: Her2 Diagnosticsmentioning

confidence: 99%

Targeting HER2-positive breast cancer: advances and future directions

Swain

Shastry

Hamilton

2022

Nat Rev Drug Discov

398

150

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The long-sought discovery of HER2 as an actionable and highly sensitive therapeutic target was a major breakthrough for the treatment of highly aggressive HER2-positive breast cancer, leading to approval of the first HER2-targeted drug -the monoclonal antibody trastuzumab -almost 25 years ago. Since then, progress has been swift and the impressive clinical activity across multiple trials with monoclonal antibodies, tyrosine kinase inhibitors and antibody-drug conjugates that target HER2 has spawned extensive efforts to develop newer platforms and more targeted therapies. This Review discusses the current standards of care for HER2-positive breast cancer, mechanisms of resistance to HER2targeted therapy and new therapeutic approaches and agents, including Nature Reviews Drug Discovery Review articlethan half of patients with metastatic HER2 + disease are diagnosed de novo, further demonstrating that most patients presenting with early disease are cured 6 .However, despite this success, metastatic HER2 + tumours inevitably develop resistance, leading to disease progression. As such, the goal of therapy in HER2 + BC is to expand the number of patients cured in the early setting and prevent recurrence. In those HER2 + cancers that do present with de novo stage IV disease or ultimately recur, development of novel therapies is needed as these tumours continue to be dependent on HER2 signalling. Therefore, extensive research is ongoing in the preclinical, translational and clinical arenas to develop original and more potent therapies for this exceptionally sensitive target, HER2.Advances in targeting HER2 include further exploitation of antibody-drug conjugates (ADCs), altering the linkers, payload or antibody scaffold to optimize efficacy 7,8 . Another approach is the development of bispecific antibodies, which use binding of two different HER2 epitopes to maximize efficacy 9 . As immunotherapy has shown benefit in triple-negative breast cancer (TNBC), attempts to mobilize the immune system in HER2 + disease are also ongoing. Immunotherapy is being approached from various angles including administering

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Section: Her2 Diagnosticsmentioning

confidence: 99%

Targeting HER2-positive breast cancer: advances and future directions

Swain

Shastry

Hamilton

2022

Nat Rev Drug Discov

398

150

View full text Add to dashboard Cite

show abstract

“…Recently, the 3rd generation of HER2-targeting ADCs have put into question the categorical classification of HER2+ BC mainly with the results of DESTINY-Breast04 showing meaningful activity in patients with HER2-low expression [ 59 ]. Thus, the traditional HER2 testing assays (IHC and ISH) need to be accompanied by more sensitive methods that better quantify the levels of HER2 required for response to T-DXd or other HER2-targeting ADCs [ 82 ].…”

Section: Perspectivesmentioning

confidence: 99%

Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer

Rassy¹,

Rached²,

Pistilli³

2022

The Breast

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“…The use of deep learning-based image analysis removes some, but not all of these limitations. Moutafi [23,24]. But also here, caution and much more efforts are needed to develop and standardise deep-learning approaches that can be extrapolated to different hospital settings, since there is still no HER2-deep learning assay available that has demonstrated robustness if implemented in different hospital settings.…”

Section: Proposed Solutions To Improve the Her2-low Assay Narrativementioning

confidence: 99%