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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Quantification of HER family receptors in breast cancer
Paolo Nuciforo1,2, Nina Radosevic-Robin3,4, Tony Ng5,6,7
1Molecular Oncology Laboratory, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, Barcelona, 08035, Spain. pnuciforo@vhio.net.
Abstract:
The clinical success of trastuzumab in breast cancer taught us that appropriate tumor evaluation is mandatory for the correct identification of patients eligible for targeted therapies. Although HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH) assays are routinely used to select patients to receive trastuzumab, both assays only partially predict response to the drug. In the case of epidermal growth factor receptor (EGFR), the link between the presence of the receptor or its amplification and response to anti-EGFR therapies could not be demonstrated. Even less is known for HER3 and HER4, mainly due to lack of robust and validated assays detecting these proteins. It is becoming evident that, besides FISH and IHC, we need better assays to quantify HER receptors and categorize the patients for individualized treatments. Here, we present the current available methodologies to measure HER family receptors and discuss the clinical implications of target quantification.
Insights
Accurate measurement of HER family receptors is crucial for predicting patient response to targeted therapies. Current methods like IHC and FISH are insufficient, necessitating improved assays for personalized cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Trastuzumab's success highlights the need for precise patient selection in targeted cancer therapy.
- Current assays for HER2 (immunohistochemistry and FISH) incompletely predict response to trastuzumab.
- The relationship between EGFR, HER3, and HER4 expression/amplification and response to targeted therapies remains unclear due to assay limitations.
Purpose of the Study:
- To review existing methodologies for quantifying HER family receptors (HER2, EGFR, HER3, HER4).
- To discuss the clinical implications of accurately quantifying these receptors for personalized medicine.
- To emphasize the need for improved assays beyond current IHC and FISH methods.
Main Methods:
- Review of current literature on HER receptor detection and quantification assays.
- Analysis of the predictive value of existing assays for targeted therapy response.
- Discussion of emerging and validated assay technologies.
Main Results:
- Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard but limited in predicting response to HER-targeted therapies.
- Quantification of HER receptors beyond simple presence or amplification is necessary for better patient stratification.
- Lack of robust assays for HER3 and HER4 hinders their clinical utility.
Conclusions:
- Improved assays are essential for accurate HER receptor quantification and patient selection for targeted therapies.
- Quantifying HER family receptors is key to advancing personalized oncology.
- Further development and validation of assays for HER3 and HER4 are critically needed.

