Novel Basis Identified For Tamoxifen Failure

Main Category: Breast Cancer
Also Included In: Endocrinology
Article Date: 04 Dec 2008 - 5:00 PDT

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Tamoxifen may worsen breast cancer in a small subset of patients. Research published in BioMed Central's open access journal Breast Cancer Research suggests that in patients who show reduced or absent expression of the protein E-cadherin, commonly used anti-oestrogen drugs such as tamoxifen may promote more harmful cancer cell behaviour.

A team of researchers co-ordinated by Dr. Stephen Hiscox, from the Welsh School of Pharmacy at Cardiff University, investigated the selective oestrogen receptor modulator (SERM) tamoxifen on human breast cancer cells, comparing it to the direct effects of oestrogen withdrawal. Dr. Hiscox said, "Anti-oestrogens, such as tamoxifen, have been the mainstay of therapy in patients with oestrogen receptor positive (ER+) breast cancer and have provided significant improvements in survival. Our experimental studies suggest that in a certain group of patients, it may be much less effective, however, as it appear to promote an aggressive cell behaviour".

The authors found that tamoxifen can promote an invasive phenotype in ER+ breast cancer cells under conditions of poor cell-cell contact, a previously unknown effect of this drug. According to Dr. Hiscox, "This could have major clinical implications for those patients with tumours where there is inherently poor intercellular adhesion. In such patients, oestrogen deprivation with aromatase inhibitors (AIs) may be a more appropriate treatment".

E-cadherin is an intercellular adhesion protein important for maintenance of cell-cell adhesion and tissue integrity. The presence of functional oestrogen receptors has been shown to be necessary for its expression.

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Notes:

1. Antioestrogens but not oestrogen deprivation promote cellular invasion in intercellular-adhesion deficient breast cancer cells.
Annabel Borley, Stephen Hiscox, Julia Gee, Chris Smith, Victoria Shaw, Peter Barrett-Lee and Robert I Nicholson
Breast Cancer Research (in press)
Article available at journal website: http://breast-cancer-research.com/
All articles are available free of charge, according to BioMed Central's open access policy.

2. Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, commentaries and reports. Research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition, the journal publishes clinical studies with a biological basis, including Phase I and Phase II trials.

3. Cardiff University is recognised in independent government assessments as one of Britain's leading teaching and research universities. It is also ranked as one of the world's top 100 universities by the Times Higher Education (THE). 2008 marks the 125th anniversary of Cardiff University having been founded by Royal Charter in 1883.

Today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University's breadth of expertise in research and research-led teaching encompasses: the humanities; the natural, physical, health, life and social sciences; engineering and technology; preparation for a wide range of professions; and a longstanding commitment to lifelong learning. Cardiff is a member of the Russell Group of the UK's leading research universities. Visit the University website at: http://www.cardiff.ac.uk

4. BioMed Central (http://www.biomedcentral.com/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.

Source: Graeme Baldwin
BioMed Central

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