Genes Associated With Breast Cancer Metastatic to Bone

The biology of tumors relapsing to bone is poorly understood. In this study, we initiated a search for genes that are implicated in tumors relapsing to bone in breast cancer. We analyzed 107 primary breast tumors in patients who were all lymph node negative at the time of diagnosis and all had exper...

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Veröffentlicht in:Journal of clinical oncology 2006-05, Vol.24 (15), p.2261-2267
Hauptverfasser: SMID, Marcel, YIXIN WANG, KLIJN, Jan G. M, SIEUWERTS, Anieta M, YI ZHANG, ATKINS, David, MARTENS, John W. M, FOEKENS, John A
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container_end_page 2267
container_issue 15
container_start_page 2261
container_title Journal of clinical oncology
container_volume 24
creator SMID, Marcel
YIXIN WANG
KLIJN, Jan G. M
SIEUWERTS, Anieta M
YI ZHANG
ATKINS, David
MARTENS, John W. M
FOEKENS, John A
description The biology of tumors relapsing to bone is poorly understood. In this study, we initiated a search for genes that are implicated in tumors relapsing to bone in breast cancer. We analyzed 107 primary breast tumors in patients who were all lymph node negative at the time of diagnosis and all had experienced relapse. Total RNA isolated from frozen tumor samples was used to gather gene expression data using oligo microarrays. A panel of 69 genes was found significantly differentially expressed between patients who experienced relapse to bone versus those who experienced relapse elsewhere in the body. The most differentially expressed gene, TFF1, was confirmed by quantitative reverse transcriptase polymerase chain reaction in an independent cohort (n = 122; P = .0015). Our differentially expressed genes, combined with a recently reported gene set relevant to tumors relapsing to bone in an animal model system, pointed to the involvement of the fibroblast growth factor receptor signaling pathway in preference of tumor cells that relapse to bone. Given that patients who experience relapse to bone may benefit from bisphosphonate therapy, we developed a classifier of 31 genes, which in an independent validation set correctly predicts all tumors relapsing to bone with a specificity of 50%. Our study identifies a panel of genes relevant to bone metastasis in breast cancer. The subsequently developed classifier of tumors relapsing to bone could, after thorough confirmation on an extended number of independent samples, and in combination with our previously developed high-risk profile, provide a diagnostic tool for the recommendation of adjuvant bisphosphonate therapy in addition to endocrine therapy or chemotherapy.
doi_str_mv 10.1200/JCO.2005.03.8802
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ispartof Journal of clinical oncology, 2006-05, Vol.24 (15), p.2261-2267
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source MEDLINE; American Society of Clinical Oncology; EZB Electronic Journals Library
subjects Adult
Aged
Biological and medical sciences
Bone Neoplasms - genetics
Bone Neoplasms - secondary
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Female
Gene Expression Profiling
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Middle Aged
Neoplasm Metastasis - genetics
Oligonucleotide Array Sequence Analysis
Peptides
Predictive Value of Tests
Risk
Trefoil Factor-1
Trefoil Factor-2
Tumor Suppressor Proteins - genetics
Tumors
title Genes Associated With Breast Cancer Metastatic to Bone
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