Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2009

01-01-2009 | Preclinical Study

Integrated gene expression profile predicts prognosis of breast cancer patients

Authors: Lian-Fang Li, Xiao-Jing Xu, Ying Zhao, Zhe-Bing Liu, Zhen-Zhou Shen, Wei-Rong Jin, Zhi-Ming Shao

Published in: Breast Cancer Research and Treatment | Issue 2/2009

Login to get access

Abstract

Gene expression data has in recent years demonstrated the superior capacity to predict the prognosis of breast cancer patients unreceiving adjuvant chemotherapy comparing to the information available from traditional clinical and pathological sources. Meanwhile, adjuvant chemotherapy can significantly improve survival of breast cancer. It would be inappropriate to ignore its effect on prognosis. We hypothesized that an integrated gene expression profile can predict the prognosis of breast cancer patients receiving chemotherapy. Therefore, we screened the specific gene markers and constructed an integrated 24-gene signature by low-density microarray including the “poor signature” and genes related to resistance to chemotherapy. The gene signature stratified correctly patients into good prognosis group and poor prognosis group. In addition, the Kaplan–Meier analyses for disease-free survival as a function of the 24-gene signature showed highly significant differences between the two groups (Log Rank test P < 0.0001 = Univariate and multivariate Cox’s proportional-hazards regression analyses indicated that the signature represents the strongest independent prognostic factor for breast cancer patients. When compared with single signature, such as Oncotype DX™ and 70 poor signature, the integrated signature showed more predominant power of predication in breast cancer patients receiving chemotherapy. Such integrated signature will critically aid clinical decision making at the level of individualization for most breast cancer patients receiving chemotherapy.
Literature
1.
go back to reference Fisher B, Jeong JH, Bryant J et al (2004) Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet 364:858–868PubMedCrossRef Fisher B, Jeong JH, Bryant J et al (2004) Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet 364:858–868PubMedCrossRef
2.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717CrossRef Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365:1687–1717CrossRef
3.
go back to reference Van’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536CrossRef Van’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536CrossRef
4.
go back to reference Wang Y, Klijn JG, Zhang Y (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679PubMed Wang Y, Klijn JG, Zhang Y (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679PubMed
5.
go back to reference Paik S, Shak S, Tang G (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826PubMedCrossRef Paik S, Shak S, Tang G (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826PubMedCrossRef
6.
go back to reference Saeki T, Tsuruo T, Sato W et al (2005) Drug resistance in chemotherapy for breast cancer. Cancer Chemother Pharmacol 56(Suppl 1):s84–s89CrossRef Saeki T, Tsuruo T, Sato W et al (2005) Drug resistance in chemotherapy for breast cancer. Cancer Chemother Pharmacol 56(Suppl 1):s84–s89CrossRef
7.
go back to reference David J, Stacey L, Zachary Veitch et al (2006) cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance. Breast Cancer Res Treat 96:17–39CrossRef David J, Stacey L, Zachary Veitch et al (2006) cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance. Breast Cancer Res Treat 96:17–39CrossRef
8.
go back to reference Andy JM, Gaorav PG, Peter MS et al (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524CrossRef Andy JM, Gaorav PG, Peter MS et al (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524CrossRef
9.
go back to reference Kang Y, Siegel PM, Shu W et al (2005) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549CrossRef Kang Y, Siegel PM, Shu W et al (2005) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549CrossRef
10.
go back to reference Li D, Hou Y, Wu J et al (2006) Gene expression profile analysis of an isogenic tumour metastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis. Eur J Cancer 42: 3274–3286PubMedCrossRef Li D, Hou Y, Wu J et al (2006) Gene expression profile analysis of an isogenic tumour metastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis. Eur J Cancer 42: 3274–3286PubMedCrossRef
11.
go back to reference Cleator S, Tsimelzon A, Ashworth A et al (2006) Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) response and resistance. Breast Cancer Res Treat 95:229–233PubMedCrossRef Cleator S, Tsimelzon A, Ashworth A et al (2006) Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) response and resistance. Breast Cancer Res Treat 95:229–233PubMedCrossRef
12.
go back to reference Heyer BS, Kochanowski H, Solter D (1999) Expression of Melk, a new protein kinase, during early mouse development. Dev Dyn 215:344–351PubMedCrossRef Heyer BS, Kochanowski H, Solter D (1999) Expression of Melk, a new protein kinase, during early mouse development. Dev Dyn 215:344–351PubMedCrossRef
13.
go back to reference Lin M-L, Park J-H, Nishidate T et al (2007) Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. Breast Cancer Res 9:R17PubMedCrossRef Lin M-L, Park J-H, Nishidate T et al (2007) Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. Breast Cancer Res 9:R17PubMedCrossRef
14.
go back to reference Pusztai L, Krishnamurti S, Perez Cardona J et al (2004) Expression of BAG-1 and BcL-2 proteins before and after neoadjuvant chemotherapy of locally advanced breast cancer. Cancer Invest 22:248–256PubMedCrossRef Pusztai L, Krishnamurti S, Perez Cardona J et al (2004) Expression of BAG-1 and BcL-2 proteins before and after neoadjuvant chemotherapy of locally advanced breast cancer. Cancer Invest 22:248–256PubMedCrossRef
15.
go back to reference Tang SC, Beck J, Murphy S et al (2004) BAG-1 expression correlates with Bcl-2, p53, differentiation, estrogen and progesterone receptors in invasive breast carcinoma. Breast Cancer Res Treat 84:203–213PubMedCrossRef Tang SC, Beck J, Murphy S et al (2004) BAG-1 expression correlates with Bcl-2, p53, differentiation, estrogen and progesterone receptors in invasive breast carcinoma. Breast Cancer Res Treat 84:203–213PubMedCrossRef
Metadata
Title
Integrated gene expression profile predicts prognosis of breast cancer patients
Authors
Lian-Fang Li
Xiao-Jing Xu
Ying Zhao
Zhe-Bing Liu
Zhen-Zhou Shen
Wei-Rong Jin
Zhi-Ming Shao
Publication date
01-01-2009
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-008-9925-4

Other articles of this Issue 2/2009

Breast Cancer Research and Treatment 2/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine