Switching Breast Cancer Drugs Reduces Relapse

An international trial has shown that switching from tamoxifen to exemestane afer 2 to 3 years increases disease-free survival and shows a slightly reduced risk of death for women treated for early stage hormone-sensitive breast cancer.

The study is published in the online edition of The Lancet.

The research is a UK analysis of data from a large international study known as the Intergroup Exemestane Study (IES).

The IES was set up to verify the anticipated benefit for patients with early breast cancer of switching from tamoxifen to the aromatase inhibitor exemestane. The scientists already had a hunch that the switch would improve disease free survival and reduce side effects by limiting prolonged exposure to either drug.

The IES data covers more than 10,000 women who have undergone treatment for early hormone sensitive ("endocrine-responsive") breast cancer and whose overall median follow up period was nearly 5 years.

In fact, because the disease free survival improvement became apparent quite early, the data from the IES trial was released early, thus giving the UK research team, comprising Charles Coombes of Imperial College London, and colleagues from The UK's Institute of Cancer Research, the opportunity to analyse it.

Their analysis included the records of 4,724 postmenopausal patients who were disease-free after 2 to 3 years on tamoxifen. Using random assignment, 2,352 women were switched to exemestane, and 2,372 stayed on taomxifen for the rest of the 5 year treatment period.

The scientists looked for evidence of persistent post-treatment, disease-free survival and any long term adverse effects.

The analysis came up with two results. First the anticipated benefit of switching was proven - the risk of relapse was lower for those women who switched.

The number of events related to disease-free survival was 32 per cent reduced in the group that switched compared to the group that did not.

And secondly, after excluding those patients who were estrogen-receptor-negative, the figures also showed that switching to exemestane after 2 to 3 years conferred a modest improvement in overall survival.

In a commentary in the same issue of the journal, Francesco Boccardo and Alessandra Rubagotti (National Cancer Institute and University of Genoa Medical School, Genoa, Italy) said that "These findings provide some limited evidence to advise all women being administered tamoxifen to switch, even though this approach is not devoid of potentially serious side-effects."

They added that the incidence of the side effects was low and "the available data do not indicate any increase in the risk of death unrelated to breast cancer in the women switched to aromatase inhibitors."

In the UK study disease-free survival was defined as "survival free of local and distant breast cancer recurrence, new primary breast cancer, and death without disease relapse".

In a note accompanying their press release, The Lancet mentions that concerns have been raised about the effects of aromatase inhibitors (for example exemestane) on bone loss and the cardiovascular system.

To understand how tamoxifen and exemestane work, one has to look at the role that estrogen plays in the growth of breast tissue.

Estrogen is a hormone that promotes the growth of breast tissue. It docks onto receptors on the surface of breast tissue cells and signals them to divide and grow. Unfortunately it also does this to cancerous cells.

Tamoxifen and exemestane reduce the effect of estrogen in two ways.

Exemestane is an aromatase inhibitor, it slows down the action of aromatase, an enzyme that changes androgens into estrogens.

Tamoxifen is an estrogen receptor modulator, it behaves like estrogen in that it docks onto the receptors on the surface of breast cells but it does not signal the cells to divide. So by competing with natural estrogen it reduces the effect of estrogen and inhibits growth of breast tissue, including the tumours.

"Survival and safety of exemestane versus tamoxifen after 2 - 3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial."
RC Coombes, LS Kilburn, CF Snowdon, R Paridaens, RE Coleman, SE Jones, J Jassem, CJH Van de Velde, T Delozier, I Alvarez, L Del Mastro, O Ortmann, K Diedrich, AS Coates, E Bajetta, SB Holmberg, D Dodwell, E Mickiewicz, J Andersen, PE LГёnning, G Cocconi, J Forbes, M Castiglione, N Stuart, A Stewart, LJ Fallowfield, G Bertelli, E Hall, RG Bogle, M Carpentieri, E Colajori, M Subar, E Ireland and JM Bliss.
The Lancet Early Online Publication, 13 February 2007
DOI:10.1016/S0140-6736(07)60200-1

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Written by: Catharine Paddock
Writer: Medical News Today