Related Experiment Video

Updated: May 11, 2026

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells
05:02

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Published on: February 4, 2021

Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases

Ina Hohensee1, Katrin Lamszus, Sabine Riethdorf

  • 1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The American Journal of Pathology
|May 14, 2013
PubMed

Insights

Targeted therapies for brain metastases in breast cancer (BC) are needed. Genetic alterations in human epidermal growth factor 2 (HER2) or epidermal growth factor receptor (EGFR)/phosphatase and tensin homologue (PTEN) pathways identify high-risk BC patients for brain metastases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Standard systemic therapies for breast cancer (BC) with brain metastases show limited efficacy.
  • Targeted therapies focusing on human epidermal growth factor receptors are of clinical interest due to their frequent alterations in BC.
  • Understanding genetic alterations in primary tumors can predict the risk of developing brain metastases.

Purpose of the Study:

  • To investigate the role of genetic alterations in epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), phosphatase and tensin homologue (PTEN), and PI3K catalytic subunit (PIK3CA) in breast cancer brain metastases.
  • To identify specific genetic alterations associated with an increased risk of developing brain metastases in breast cancer patients.
  • To explore potential therapeutic targets for breast cancer brain metastases.

Main Methods:

  • Analysis of copy number, mutation status, and protein expression of EGFR, HER2, PTEN, and PIK3CA.
  • Examination of 110 ductal carcinoma in situ, primary tumor, and metastatic BC samples, including brain metastases.
  • Comparison of genetic alterations between brain metastases and primary tumors, bone relapse, or other distant metastases.

Main Results:

  • Significantly higher frequencies of EGFR, HER2, and PTEN alterations were observed in breast cancer brain metastases compared to other metastatic sites or good prognosis primary tumors.
  • Primary tumors with subsequent brain relapse exhibited high frequencies of EGFR and PTEN alterations.
  • PIK3CA alterations were not associated with an increased risk of brain metastases. Genetic alterations in EGFR and PTEN were common in triple-negative BC.
  • HER2 alterations were rarely seen in patients with EGFR/PTEN alterations.

Conclusions:

  • Two independent high-risk primary breast cancer subgroups for developing brain metastases were identified: those with HER2 alterations and those with EGFR/PTEN alterations.
  • These specific genetic alterations were not associated with an increased risk of bone metastasis.
  • The findings highlight HER2 and EGFR/PTEN pathways as potential therapeutic targets for treating breast cancer brain metastases.

More Related Videos

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis07:43

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis

Published on: February 8, 2017

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging06:44

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging

Published on: June 7, 2020

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Targeted Cancer Therapies02:57

Targeted 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...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...