Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.

Tobias Grob; Uwe Heilenkötter; Stefan Geist; Peter Paluchowski; Christian Wilke; Fritz Jänicke; Alexander Quaas; Waldemar Wilczak; Matthias Choschzick; Guido Sauter; Annette Lebeau

Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.

Standard

Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer. / Grob, Tobias; Heilenkötter, Uwe; Geist, Stefan; Paluchowski, Peter; Wilke, Christian; Jänicke, Fritz; Quaas, Alexander; Wilczak, Waldemar; Choschzick, Matthias; Sauter, Guido ; Lebeau, Annette.

In: BREAST CANCER RES TR, Vol. 134, No. 2, 2, 2012, p. 561-567.

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

Harvard

Grob, T, Heilenkötter, U, Geist, S, Paluchowski, P, Wilke, C, Jänicke, F, Quaas, A, Wilczak, W, Choschzick, M, Sauter, G & Lebeau, A 2012, 'Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.', BREAST CANCER RES TR, vol. 134, no. 2, 2, pp. 561-567. <http://www.ncbi.nlm.nih.gov/pubmed/22610646?dopt=Citation>

APA

Grob, T., Heilenkötter, U., Geist, S., Paluchowski, P., Wilke, C., Jänicke, F., Quaas, A., Wilczak, W., Choschzick, M., Sauter, G., & Lebeau, A. (2012). Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer. BREAST CANCER RES TR, 134(2), 561-567. [2]. http://www.ncbi.nlm.nih.gov/pubmed/22610646?dopt=Citation

Vancouver

Grob T, Heilenkötter U, Geist S, Paluchowski P, Wilke C, Jänicke F et al. Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer. BREAST CANCER RES TR. 2012;134(2):561-567. 2.

Bibtex

@article{e4b73c0005f140f0adba017cd62967cf,

title = "Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.",

abstract = "Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.",

keywords = "Adult, Humans, Aged, Female, Middle Aged, Aged, 80 and over, DNA Mutational Analysis, Base Sequence, Gene Dosage, Gene Amplification, In Situ Hybridization, Fluorescence, Tissue Array Analysis, Receptor, Epidermal Growth Factor/genetics, Tumor Suppressor Protein p53/genetics, Receptors, Progesterone/metabolism, *Oncogenes, *Mutation, Receptor Protein-Tyrosine Kinases/genetics, Receptors, Estrogen/metabolism, Proto-Oncogene Proteins B-raf/genetics, Proto-Oncogene Proteins/genetics, Breast Neoplasms/drug therapy/*genetics/metabolism, Carcinoma, Ductal, Breast/drug therapy/*genetics/metabolism, Receptor, erbB-2/genetics/metabolism, ras Proteins/genetics, Adult, Humans, Aged, Female, Middle Aged, Aged, 80 and over, DNA Mutational Analysis, Base Sequence, Gene Dosage, Gene Amplification, In Situ Hybridization, Fluorescence, Tissue Array Analysis, Receptor, Epidermal Growth Factor/genetics, Tumor Suppressor Protein p53/genetics, Receptors, Progesterone/metabolism, *Oncogenes, *Mutation, Receptor Protein-Tyrosine Kinases/genetics, Receptors, Estrogen/metabolism, Proto-Oncogene Proteins B-raf/genetics, Proto-Oncogene Proteins/genetics, Breast Neoplasms/drug therapy/*genetics/metabolism, Carcinoma, Ductal, Breast/drug therapy/*genetics/metabolism, Receptor, erbB-2/genetics/metabolism, ras Proteins/genetics",

author = "Tobias Grob and Uwe Heilenk{\"o}tter and Stefan Geist and Peter Paluchowski and Christian Wilke and Fritz J{\"a}nicke and Alexander Quaas and Waldemar Wilczak and Matthias Choschzick and Guido Sauter and Annette Lebeau",

year = "2012",

language = "English",

volume = "134",

pages = "561--567",

journal = "BREAST CANCER RES TR",

issn = "0167-6806",

publisher = "Springer New York",

number = "2",

}

RIS

TY - JOUR

T1 - Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.

AU - Grob, Tobias

AU - Heilenkötter, Uwe

AU - Geist, Stefan

AU - Paluchowski, Peter

AU - Wilke, Christian

AU - Jänicke, Fritz

AU - Quaas, Alexander

AU - Wilczak, Waldemar

AU - Choschzick, Matthias

AU - Sauter, Guido

AU - Lebeau, Annette

PY - 2012

Y1 - 2012

N2 - Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.

AB - Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.

KW - Adult

KW - Humans

KW - Aged

KW - Female

KW - Middle Aged

KW - Aged, 80 and over

KW - DNA Mutational Analysis

KW - Base Sequence

KW - Gene Dosage

KW - Gene Amplification

KW - In Situ Hybridization, Fluorescence

KW - Tissue Array Analysis

KW - Receptor, Epidermal Growth Factor/genetics

KW - Tumor Suppressor Protein p53/genetics

KW - Receptors, Progesterone/metabolism

KW - Oncogenes

KW - Mutation

KW - Receptor Protein-Tyrosine Kinases/genetics

KW - Receptors, Estrogen/metabolism

KW - Proto-Oncogene Proteins B-raf/genetics

KW - Proto-Oncogene Proteins/genetics

KW - Breast Neoplasms/drug therapy/genetics/metabolism

KW - Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism

KW - Receptor, erbB-2/genetics/metabolism

KW - ras Proteins/genetics