TITLE

Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen

AUTHOR(S)
Loi, Sherene; Haibe-Kains, Benjamin; Desmedt, Christine; Wirapati, Pratyaksha; Lallemand, Françoise; Tutt, Andrew M.; Gillet, Cheryl; Ellis, Paul; Ryder, Kenneth; Reid, James F.; Daidone, Maria G.; Pierotti, Marco A.; Berns, Els M. J. J.; Jansen, Maurice P. H. M.; Foekens, John A.; Delorenzi, Mauro; Bontempi, Gianluca; Piccart, Martine J.; Sotiriou, Christos
PUB. DATE
January 2008
SOURCE
BMC Genomics;2008, Vol. 9, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings. Results: We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95%CI: 1.29-3.13; p = 0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response. Conclusion: We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen.
ACCESSION #
38122819

 

Related Articles

  • Molecular functions and significance of the MTA family in hormone-independent cancer. Ning, Zhifeng; Gan, Jinfeng; Chen, Chaoying; Zhang, Dianzheng; Zhang, Hao // Cancer & Metastasis Reviews;Dec2014, Vol. 33 Issue 4, p901 

    The members of the metastasis-associated protein (MTA) family play pivotal roles in both physiological and pathophysiological processes, especially in cancer development and metastasis, and their role as master regulators has come to light. Due to the fact that they were first identified as...

  • Alternations of ER, PR, HER-2/neu, and P53 protein expression in ductal breast carcinomas and clinical implications. Liu, Caigang; Zhang, Hao; Shuang, Chen; Lu, Yang; Jin, Feng; Xu, Huimian; Lu, Ping // Medical Oncology;Sep2010, Vol. 27 Issue 3, p747 

    The aim of the study is to investigate the alterations in expression of estrogen receptor alpha (ER), progesterone receptor (PgR), c-erbB2 gene (HER-2/neu), and P53 protein in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC), and the association between...

  • CCNA2 Is a Prognostic Biomarker for ER+ Breast Cancer and Tamoxifen Resistance. Gao, Tian; Han, Yong; Yu, Ling; Ao, Sheng; Li, Ziyu; Ji, Jiafu // PLoS ONE;Mar2014, Vol. 9 Issue 3, p1 

    Identification of effective prognostic biomarkers and targets are of crucial importance to the management of estrogen receptor positive (ER+) breast cancer. CCNA2 (also known as CyclinA2) belongs to the highly conserved cyclin family and is significantly overexpressed in various cancer types. In...

  • Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer. J B Arnes // Journal of Clinical Pathology;Feb2009, Vol. 62 Issue 2, p139 

    AIMS: BRCA1-related breast cancer is associated with a basal-like phenotype, and is frequently oestrogen receptor (ER) and HER2 negative. The expression of epidermal growth factor receptor (EGFR) has been considered to be one component of the basal-like phenotype, but no standard criteria exist....

  • Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas. Dueñas Jiménez, J.; Candanedo Arellano, A.; Santerre, A.; Orozco Suárez, S.; Sandoval Sánchez, H.; Feria Romero, I.; López-Elizalde, R.; Alonso Venegas, M.; Netel, B.; Torre Valdovinos, B.; Dueñas Jiménez, S. // Journal of Neuro-Oncology;Sep2014, Vol. 119 Issue 2, p275 

    Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERβ)....

  • Tamoxifen and its New Derivatives in Cancer Research. Rivera-Guevara, Claudia; Camacho, Javier // Recent Patents on Anti-Cancer Drug Discovery;May2011, Vol. 6 Issue 2, p237 

    A major challenge in cancer research is to discover drugs with high selectivity and minor side-effects. Tamoxifen has been widely used for more than 30 years in breast cancer treatment and prevention. Tamoxifen acts mainly via estrogen receptors (ER), but also displays anti-tumor activity in...

  • HDAC inhibitor may overcome resistance to common breast cancer drug.  // Biomedical Market Newsletter;11/14/2011, Vol. 21, p253 

    The article presents research led by Pamela N. Munster of the University of California, San Francisco on how estrogen receptor-positive breast cancer tumors become resistant to tamoxifen, a hormonal therapy for premenopausal patients with the type of cancer. The research found out that estrogen...

  • Development and Validation of Therapeutically Relevant Multi-Gene Biomarker Classifiers. Simon, Richard // JNCI: Journal of the National Cancer Institute;6/15/2005, Vol. 97 Issue 12, p866 

    Attempts to provide possible explanations for the inconsistency of results of a June 2004 study on a two-gene expression ratio that authors claimed accurately predicted clinical outcome of early-stage breast cancer patients treated with adjuvant tamoxifen monotherapy and a 2005 study that failed...

  • Prognostic Discrimination Using a 70-Gene Signature among Patients with Estrogen Receptor-Positive Breast Cancer and an Intermediate 21-Gene Recurrence Score. Sung Gwe Ahn; Hak Min Lee; Hak Woo Lee; Seung Ah Lee; Se-Ra Lee; Sun-Hee Leem; Joon Jeong; In-Sun Chu // International Journal of Molecular Sciences;Dec2013, Vol. 14 Issue 12, p23658 

    The Oncotype DX® recurrence score (RS) predictor has been clinically utilized to appropriately select adjuvant chemotherapy for patients with estrogen receptor (ER)-positive early breast cancer. However, the selection of chemotherapy for patients with intermediate RSs remains controversial....

Share

Read the Article

Courtesy of NEW JERSEY STATE LIBRARY

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics