Switching drugs improves breast cancer patient survival rates

Changing to an aromatase inhibitor called exemestane after two to three years of tamoxifen treatment can cut women’s risk of dying from breast cancer, according to long-term follow up data from the Intergroup Exemestane Study (IES) published today in the Journal of Clinical Oncology.

Until recently, most women diagnosed with early stage oestrogen receptor-positive (ER+ or hormone sensitive) breast cancer were given tamoxifen for around five years after surgery to help prevent the disease coming back. This therapy was once viewed as the ‘gold-standard’ treatment and it has been shown to cut the risk of death by 34 per cent. However, over recent years, increasing numbers of these women are treated with aromatase inhibitors either as first-line treatment or after treatment with tamoxifen.

A large-scale trial called the Intergroup Exemestane Study (IES) was set up across 37 countries in 1998 to examine the long-term effectiveness of switching to exemestane after two to three years of tamoxifen to complete a total of five years adjuvant treatment. The study is led by The Institute of Cancer Research’s Clinical Trials & Statistics Unit (ICR-CTSU) and Imperial College London’s Clinical Trials Unit - Cancer.  The trial was funded by Pfizer Inc and both units receive support from Cancer Research UK.

Postmenopausal patients who were disease-free after two to three years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane for the remainder of the five-year period. Results published in 2007 showed that women who switched drugs had higher survival rates, however it was unclear whether this effect would continue in the years after treatment finished and whether there would be any long-term side-effects.

The analysis published today includes 4,052 patients with ER+ cancer and 547 women with tumours whose ER status is unknown.  After a median follow-up of 91 months, women who had been switched to exemestane were 18 per cent less likely to have disease recurrence and were 14 per cent less likely to have died than those who stayed on tamoxifen. Women who took exemestane experienced fewer gynaecological side-effects and more musculoskeletal side-effects while on treatment, but there was no significant difference in long-term side-effects between the groups.

Lead author Professor Judith Bliss, Director of the ICR’s Clinical Trials & Statistics Unit, says: “The long-term results from our study show that the improvements observed following the switch to exemestane are real and continue for at least five years after finishing treatment. These modest but persistent improvements in overall survival will be welcome news for the many postmenopausal women diagnosed with ER+ breast cancer.”

Principle Investigator Professor Charles Coombes, Head of Division of Cancer at Imperial College London, says: “At the start of this study we were uncertain as to whether we would encounter long-term side effects or whether any beneficial effects would be outweighed by these side-effects. As a result of this latest analysis, we can be sure that we not only benefit more women, but also that they encounter fewer serious effects such as deep vein thrombosis or uterine cancer while on treatment, when compared to women who stay on tamoxifen treatment for the entire five years.”

About 75 per cent of the 48,000 women diagnosed with breast cancer in the UK each year have an oestrogen receptor positive tumour, meaning that the hormone oestrogen is playing a role in cancer growth. Both tamoxifen and exemestane are hormone treatments: tamoxifen works by blocking the tumour’s ability to use oestrogen, while aromatase inhibitors like exemestane reduce the body's production of oestrogen.

The researchers believe that during treatment with tamoxifen, some cancer cells can become resistant to the effects of the drug. Exemestane is subsequently able to kill these resistant cells by withdrawing the oestrogen from circulation.

Dr Lesley Walker, Cancer Research UK's director of cancer information, says: “These results show that exemestane is a valuable addition to the treatment of hormone-positive breast cancer, providing a way of avoiding tamoxifen resistance and improving treatment success and survival for many women. Aromatase inhibitors like exemestane are really improving the options for breast cancer treatment and are showing great promise in the realm of breast cancer prevention too.”

For more information, visit www.icr.ac.uk

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