Originally published as JCO Early Release 10.1200/JCO.2005.03.8802 on April 24 2006
Journal of Clinical Oncology, Vol 24, No 15 (May 20), 2006: pp. 2261-2267
© 2006 American Society of Clinical Oncology.
Genes Associated With Breast Cancer Metastatic to Bone
Marcel Smid,
Yixin Wang,
Jan G.M. Klijn,
Anieta M. Sieuwerts,
Yi Zhang,
David Atkins,
John W.M. Martens,
John A. Foekens
From the Department of Medical Oncology, Erasmus MC–Daniel den Hoed, Rotterdam, the Netherlands; and Veridex LLC, a Johnson & Johnson Company, San Diego, CA
Address reprint requests to John A. Foekens, PhD, Erasmus MC, Josephine Nefkens Institute, Rm BE-426, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands; e-mail: j.foekens{at}erasmusmc.nl
PURPOSE: 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.
PATIENTS AND METHODS: 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.
RESULTS: 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%.
CONCLUSION: 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.
Supported in part by the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research. This organization had no role in study design, the collection or analysis of data, writing the article, or in decisions relating to publication.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Related Editorials
- A "Bone" Fide Predictor of Metastasis? Predicting Breast Cancer Metastasis to Bone
Scott L. Kominsky and Nancy E. Davidson
JCO 2006 24: 2227-2229
[Full Text]
- A "Bone" Fide Predictor of Metastasis? Predicting Breast Cancer Metastasis to Bone
Scott L. Kominsky and Nancy E. Davidson
JCO 2006 24: 2227-2229
[Full Text]
This article has been cited by other articles:
|
|
|
|
 
L. D. Moore, T. Isayeva, G. P. Siegal, and S. Ponnazhagan
Silencing of Transforming Growth Factor-{beta}1 In situ by RNA Interference for Breast Cancer: Implications for Proliferation and Migration In vitro and Metastasis In vivo
Clin. Cancer Res.,
August 1, 2008;
14(15):
4961 - 4970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Smid, Y. Wang, Y. Zhang, A. M. Sieuwerts, J. Yu, J. G.M. Klijn, J. A. Foekens, and J. W.M. Martens
Subtypes of Breast Cancer Show Preferential Site of Relapse
Cancer Res.,
May 1, 2008;
68(9):
3108 - 3114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chanrion, V. Negre, H. Fontaine, N. Salvetat, F. Bibeau, G. M. Grogan, L. Mauriac, D. Katsaros, F. Molina, C. Theillet, et al.
A Gene Expression Signature that Can Predict the Recurrence of Tamoxifen-Treated Primary Breast Cancer
Clin. Cancer Res.,
March 15, 2008;
14(6):
1744 - 1752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Meijer, A. M Sieuwerts, M. P Look, T. van Agthoven, J. A Foekens, and L. C J Dorssers
Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer
Endocr. Relat. Cancer,
March 1, 2008;
15(1):
101 - 111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-C. Bidard, A. Vincent-Salomon, B. Sigal-Zafrani, V. Dieras, C. Mathiot, L. Mignot, J.-P. Thiery, X. Sastre-Garau, and J.-Y. Pierga
Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells
Ann. Onc.,
March 1, 2008;
19(3):
496 - 500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Li, A. Chaudhuri, J. Chant, and Z. Tang
PADGE: analysis of heterogeneous patterns of differential gene expression
Physiol Genomics,
December 19, 2007;
32(1):
154 - 159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A.N. Rose, F. Pepin, C. Russo, J. E. Abou Khalil, M. Hallett, and P. M. Siegel
Osteoactivin Promotes Breast Cancer Metastasis to Bone
Mol. Cancer Res.,
October 1, 2007;
5(10):
1001 - 1014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lonning, S Knappskog, V Staalesen, R Chrisanthar, and J. Lillehaug
Breast cancer prognostication and prediction in the postgenomic era
Ann. Onc.,
August 1, 2007;
18(8):
1293 - 1306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Minn, G. P. Gupta, D. Padua, P. Bos, D. X. Nguyen, D. Nuyten, B. Kreike, Y. Zhang, Y. Wang, H. Ishwaran, et al.
Lung metastasis genes couple breast tumor size and metastatic spread
PNAS,
April 17, 2007;
104(16):
6740 - 6745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Kominsky and N. E. Davidson
A "Bone" Fide Predictor of Metastasis? Predicting Breast Cancer Metastasis to Bone
J. Clin. Oncol.,
May 20, 2006;
24(15):
2227 - 2229.
[Full Text]
[PDF]
|
|
|
|
