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

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Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases. / Hohensee, Ina; Lamszus, Katrin; Riethdorf, Sabine; Meyer-Staeckling, Sönke; Glatzel, Markus; Matschke, Jakob; Witzel, Isabell; Westphal, Manfred; Brandt, Burkhard; Müller, Volkmar; Pantel, Klaus; Wikman, Harriet.

In: AM J PATHOL, Vol. 183, No. 1, 01.07.2013, p. 83-95.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hohensee, I, Lamszus, K, Riethdorf, S, Meyer-Staeckling, S, Glatzel, M, Matschke, J, Witzel, I, Westphal, M, Brandt, B, Müller, V, Pantel, K & Wikman, H 2013, 'Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases', AM J PATHOL, vol. 183, no. 1, pp. 83-95. https://doi.org/10.1016/j.ajpath.2013.03.023

APA

Hohensee, I., Lamszus, K., Riethdorf, S., Meyer-Staeckling, S., Glatzel, M., Matschke, J., Witzel, I., Westphal, M., Brandt, B., Müller, V., Pantel, K., & Wikman, H. (2013). Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases. AM J PATHOL, 183(1), 83-95. https://doi.org/10.1016/j.ajpath.2013.03.023

Vancouver

Hohensee I, Lamszus K, Riethdorf S, Meyer-Staeckling S, Glatzel M, Matschke J et al. Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases. AM J PATHOL. 2013 Jul 1;183(1):83-95. https://doi.org/10.1016/j.ajpath.2013.03.023

Bibtex

@article{6eeca5e2c2d14e6bb11727f7ae2388c9,
title = "Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases",
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.",
keywords = "Bone Neoplasms, Brain Neoplasms, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, DNA Copy Number Variations, DNA Mutational Analysis, Female, Gene Expression Regulation, Neoplastic, Genes, erbB-1, Genes, erbB-2, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Mutation, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Real-Time Polymerase Chain Reaction, Tumor Markers, Biological",
author = "Ina Hohensee and Katrin Lamszus and Sabine Riethdorf and S{\"o}nke Meyer-Staeckling and Markus Glatzel and Jakob Matschke and Isabell Witzel and Manfred Westphal and Burkhard Brandt and Volkmar M{\"u}ller and Klaus Pantel and Harriet Wikman",
note = "Copyright {\textcopyright} 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2013",
month = jul,
day = "1",
doi = "10.1016/j.ajpath.2013.03.023",
language = "English",
volume = "183",
pages = "83--95",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases

AU - Hohensee, Ina

AU - Lamszus, Katrin

AU - Riethdorf, Sabine

AU - Meyer-Staeckling, Sönke

AU - Glatzel, Markus

AU - Matschke, Jakob

AU - Witzel, Isabell

AU - Westphal, Manfred

AU - Brandt, Burkhard

AU - Müller, Volkmar

AU - Pantel, Klaus

AU - Wikman, Harriet

N1 - Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

KW - Bone Neoplasms

KW - Brain Neoplasms

KW - Breast Neoplasms

KW - Carcinoma, Intraductal, Noninfiltrating

KW - DNA Copy Number Variations

KW - DNA Mutational Analysis

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Genes, erbB-1

KW - Genes, erbB-2

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization, Fluorescence

KW - Kaplan-Meier Estimate

KW - Mutation

KW - PTEN Phosphohydrolase

KW - Phosphatidylinositol 3-Kinases

KW - Real-Time Polymerase Chain Reaction

KW - Tumor Markers, Biological

U2 - 10.1016/j.ajpath.2013.03.023

DO - 10.1016/j.ajpath.2013.03.023

M3 - SCORING: Journal article

C2 - 23665199

VL - 183

SP - 83

EP - 95

JO - AM J PATHOL

JF - AM J PATHOL

SN - 0002-9440

IS - 1

ER -