Related Experiment Video
Updated: May 29, 2026
11:34
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Genetic heterogeneity in HER2 testing may influence therapy eligibility
Barbara Bernasconi1, Anna Maria Chiaravalli, Giovanna Finzi
1Department of Human Morphology, Section of Anatomic Pathology, University of Insubria and Ospedale di Circolo, Via O. Rossi, 9, 21100 Varese, Italy. barbara1.bernasconi@uninsubria.it
Breast Cancer Research and Treatment
|September 9, 2011
Summary
Accurate HER2 testing is crucial for anti-HER2 therapy selection. Investigating HER2 genetic heterogeneity with a specific FISH strategy improves patient eligibility for targeted treatments like trastuzumab.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- HER2 testing inaccuracies affect approximately 20% of cases.
- Current guidelines for HER2 testing interpretation, including heterogeneity, lack uniformity.
- The superiority of IHC versus FISH for predicting anti-HER2 therapy benefit remains unclear.
Purpose of the Study:
- To compare HER2 status determined by IHC and FISH in 291 breast cancers.
- To investigate HER2 genetic heterogeneity using a specific FISH strategy.
- To evaluate the impact of heterogeneity and polysomy on accurate HER2 assessment.
Main Methods:
- Comparative analysis of HER2 status using both IHC and FISH assays.
- Application of a specialized FISH strategy to detect genetic heterogeneity.
- Evaluation of 291 non-consecutive breast cancer cases.
Main Results:
- HER2 amplified cells exhibit diverse distribution patterns, including diffuse, clustered, intermingled, or confined to metastatic nodules.
- Accurate assessment of ratio value in the presence of genetic heterogeneity and polysomy is vital.
- Newer guidelines (CAP 2009, SIGU) identify more patients eligible for trastuzumab or lapatinib therapy compared to older guidelines (ASCO/CAP 2007).
Conclusions:
- Understanding HER2 genetic heterogeneity is essential for accurate HER2 status determination.
- A specific FISH strategy can reveal complex HER2 amplification patterns.
- Revised HER2 scoring criteria improve patient selection for targeted therapies, potentially expanding treatment eligibility.
More Related Videos
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
02:50Combination Therapies and Personalized Medicine
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...