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Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases.
- Source :
-
The American journal of pathology [Am J Pathol] 2013 Jul; Vol. 183 (1), pp. 83-95. Date of Electronic Publication: 2013 May 09. - Publication Year :
- 2013
-
Abstract
- Current standard systemic therapies for treating breast cancer patients with brain metastases are inefficient. Targeted therapies against human epidermal growth factor receptors are of clinical interest because of their alteration in a subset of breast cancers (BCs). We analyzed copy number, mutation status, and protein expression of epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), phosphatase and tensin homologue (PTEN), and PI3K catalytic subunit (PIK3CA) in 110 ductal carcinoma in situ, primary tumor, and metastatic BC samples. Alterations in EGFR, HER2, and PTEN, alone or in combination, were found in a significantly larger fraction of breast cancer brain metastases tumor tissue compared with samples from primary tumors with good prognosis, bone relapse, or other distant metastases (all P < 0.05). Primary tumor patients with a subsequent brain relapse showed almost equally high frequencies of especially EGFR and PTEN alteration as the breast cancer brain metastases patients. PIK3CA was not associated with an increased risk of brain metastases. Genetic alterations in both EGFR and PTEN were especially common in triple-negative breast cancer patients and rarely were seen among HER2-positive patients. In conclusion, we identified two independent high-risk primary BC subgroups for developing brain metastases, represented by genetic alterations in either HER2 or EGFR/PTEN-driven pathways. In contrast, none of these pathways was associated with an increased risk of bone metastasis. These findings highlight the importance of both pathways as possible targets in the treatment of brain metastases in breast cancer.<br /> (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Biomarkers, Tumor metabolism
Bone Neoplasms genetics
Bone Neoplasms secondary
Breast Neoplasms genetics
Carcinoma, Intraductal, Noninfiltrating genetics
Class I Phosphatidylinositol 3-Kinases
DNA Copy Number Variations
DNA Mutational Analysis
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Kaplan-Meier Estimate
Mutation
PTEN Phosphohydrolase genetics
PTEN Phosphohydrolase metabolism
Phosphatidylinositol 3-Kinases genetics
Phosphatidylinositol 3-Kinases metabolism
Real-Time Polymerase Chain Reaction
Biomarkers, Tumor genetics
Brain Neoplasms genetics
Brain Neoplasms secondary
Breast Neoplasms pathology
Gene Expression Regulation, Neoplastic
Genes, erbB-1
Genes, erbB-2
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 183
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23665199
- Full Text :
- https://doi.org/10.1016/j.ajpath.2013.03.023