Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

The efficacy of the antibody drug conjugate (ADC) Trastuzumab deruxtecan (T-DXd) in HER2 low breast cancer patients suggests that the historical/conventional assays for HER2 may need revision for optimal patient care. Specifically, the conventional assay is designed to distinguish amplified HER2 from unamplified cases but is not sensitive enough to stratify the lower ranges of HER2 expression. Here we determine the optimal dynamic range for unamplified HER2 detection in breast cancer and then redesign an assay to increase the resolution of the assay to stratify HER2 expression in unamplified cases. We used the AQUA™ method of quantitative immunofluorescence to test a range of antibody concentrations to maximize the sensitivity within the lower range of HER2 expression. Then, using a cell line microarray with HER2 protein measured by mass spectrometry we determined the amount of HER2 protein in units of attomols/mm2. Then by calculation of the limits of detection, quantification, and linearity of this assay we determined that low HER2 range expression in unamplified cell lines is between 2 and 20 attomol/mm2. Finally, application of this assay to a serial collection of 364 breast cancer cases from Yale shows 67% of the population has HER2 expression above the limit of quantification and below the levels seen in HER2 amplified breast cancer. In the future, this assay could be used to determine the levels of HER2 required for response to T-DXd or similar HER2 conjugated ADCs. © 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.


Myrto Moutafi, Charles J Robbins, Vesal Yaghoobi, Aileen I Fernandez, Sandra Martinez-Morilla, Vasiliki Xirou, Yalai Bai, Yan Song, Patricia Gaule, Joseph Krueger, Kenneth Bloom, Salisha Hill, Daniel C Liebler, Regan Fulton, David L Rimm. Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer. Laboratory investigation; a journal of technical methods and pathology. 2022 Oct;102(10):1101-1108

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 35595825

View Full Text