Taking a breast cancer drug called exemestane after tamoxifen can substantially reduce the chance of recurrence, according to the early results of a major new trial, co-ordinated by Cancer Research UK funded groups1.
Currently, most breast cancer patients receive a five-year course of tamoxifen following surgery to help prevent their cancer from coming back.
But, the international study involving over 4,700 post-menopausal women, found that switching to exemestane after two to three years of tamoxifen reduces the risk of breast cancer returning by a third (32 per cent) when compared with women who remained on tamoxifen for a full five years.
Researchers from the International Collaborative Cancer Group at Imperial College London and The Institute of Cancer Research led the study, which was funded by Pfizer.
The team also found the sequence of tamoxifen and exemestane was better than tamoxifen alone at cutting the chance of cancer arising in the other breast.
Cancer Research UK experts say that while the results are promising, it is essential to find out any long-term effects of the drug sequence before any firm recommendations can be made.
Exemestane is an aromatase inhibitor and works by halting the natural production of oestrogen – the hormone responsible for the development and recurrence of many breast cancers.
Lead author Professor Charles Coombes, Director of the Cancer Research UK Laboratories at Imperial College London, Hammersmith and Charing Cross Hospitals, says: “While tamoxifen can prevent recurrence in most patients there are still many who relapse within five years of diagnosis. This happens because breast cancer can become resistant to the drug. So we thought that switching from tamoxifen to an aromatase inhibitor, in this case exemestane, during a five-year course of hormone treatment could be beneficial.
“Disturbingly, in a few cases, prolonged use of tamoxifen can also result in side-effects such as blood-clotting disorders and cancer of the uterus. By cutting use of the drug to two or three years we hoped to give patients benefit while minimising the risk of long-term side-effects.”
The trial recruited 4,742 post-menopausal women between 1998 and 2003 from 37 countries, including the UK, who had undergone surgery for breast cancer and taken tamoxifen for two to three years. Half of the group continued taking tamoxifen while the other half switched to exemestane to complete a total of five years of hormone treatment. Patients were followed up for an average of two and a half years after they were randomly assigned to take exemestane or continue on tamoxifen.
Researchers found disease-free survival2 three years after randomisation was 92 per cent in patients who switched to exemestane compared with 87 per cent in patients who continued on tamoxifen.
So, for every 100 patients who continued taking tamoxifen, 13 had a recurrence within three years. The other 87 remained cancer free. For every 100 patients who switched to exemestane, eight had a recurrence within three years and the other 92 remained cancer free.
The risk of endometrial cancer was lower for women taking exemestane. In total, there were 11 cases of endometrial cancer in patients continuing tamoxifen and five in those switching to exemestane. The researchers also found exemestane lowered the incidence of blood clotting disorders when compared with tamoxifen.
More patients on exemestane reported diarrhoea and joint pains, while more women on tamoxifen reported gynaecological disorders and muscle cramps.
Prof Coombes says: “Women switching to exemestane had fewer cases of cancer in the other breast which also suggests that taking the drug after tamoxifen may be a better way to prevent breast cancer than taking tamoxifen alone. We already know tamoxifen increases the risk of endometrial cancer so a lower risk with use of exemestane is reassuring.”
Fellow author Judith Bliss, Director of the Cancer Research UK Clinical Trials and Statistics Unit at The Institute of Cancer Research, says: “Though recurrence of breast cancer in women taking tamoxifen was already low, our results show that switching to exemestane can reduce that number by a about a third.
“This study represents a real example of clinicians and scientists from around the world working together, overcoming differences in local health care practices, to conduct the trial as quickly as possible and get the information out there for future patients.
“It is essential that we continue the study as further follow-up of these patients will help us assess the long-term benefit associated with this drug sequence,” she adds.
Professor Robert Souhami, Director of Clinical and External Affairs at Cancer Research UK, says: “The results of this study are very promising and add to the growing body of evidence which suggests that aromatase inhibitors have an important role to play in breast cancer treatment.
“While this is good news, it’s important to remember that these results only tell us what happens in the short term. It’s essential that we continue to study the drug to make sure it doesn’t expose patients to any unpredicted long-term risks. We also need to find out how the drug affects overall survival and quality of life for patients. Once this is done we can judge if the switch to exemestane is of overall benefit.
“These are early results and at present exemestane is not yet routinely available for patients with early breast cancer. Women who feel they want to know more should contact their cancer specialist who can advise them on treatment options depending on their individual circumstances.”
- New England Journal of Medicine350 (11) pp.1081-92
- Disease-free survival describes the chance of a patient being alive without a recurrence of their cancer.
Exemestance reduced the risk of contralateral cancer (cancer arising in the other breast) – cases were detected in a total of 20 patients continuing tamoxifen and nine switching to exemestane.
This study was a double blind trial where neither the doctor nor the patient know which treatment the patient is having. The study was led by the International Collaborative Cancer Group but has involved participation from 20 academic collaborative trials groups from around the world under the umbrella of the Breast International Group.
The International Collaborative Cancer Group is based at Imperial College London, UK, and the Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK. Cancer Research UK funds the Clinical Trials and Statistics Unit at The Institute of Cancer Research and supports the work of Professor Charles Coombes, the principal investigator on this study.
The Clinical Trials and Statistics Unit at The Institute of Cancer Research is an accredited trials unit of the National Cancer Research Institute.
Pfizer were the sponsors of the study and provided research funding to allow the study to be conducted.
The drug exemestane is manufactured by Pfizer under the trade name Aromasin.
The trial was investigator led. It was designed, the data managed and the analysis performed, independently of Pfizer.
Tamoxifen works by blocking the function of molecules called oestrogen receptors (ER). Tamoxifen is usually prescribed for women who have been found to have oestrogen receptors (ER positive) or progesterone receptors in their breast cancer cells.
Last year, a Canadian study found an aromatase inhibitor called letrozole could reduce the risk of breast cancer recurrence in women who have completed a five-year course of tamoxifen as compared with a placebo.
In 2002, a Cancer Research UK study found that in women newly diagnosed with breast cancer, treatment with an aromatase inhibitor called anastrozole (trade name Arimidex) gave a 17 per cent lower risk of breast cancer recurrence and contralateral breast cancer (cancer arising in the other breast) than tamoxifen in patients who respond to hormone treatment. This study did not look at the sequencing of treatments.
Breast cancer affects around 40,700 women each year in the UK.
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The following UK centres took part in the study:
North Staffordshire Royal Infirmary, Stoke-on-Trent; Charing Cross Hospital, London; Lincoln & Louth NHS Trust County Hospital, Lincoln; Hinchingbrooke Hospital, Cambridgeshire; Yeovil Hospital, Somerset, Taunton & Somerset NHS Trust; Walsgrave Hospital, Coventry; Princess Royal Hospital,Telford, Shropshire; Royal Free Hospital, London; Whittington Hospital, London; Luton and Dunstable Hospital, Luton; Mount Vernon Hospital, Middlesex; St. Georges Hospital, London; Belfast City Hospital, Belfast; St Margaret’s Hospital, Essex; Royal Shrewsbury Hospital, Shrewsbury; North Middlesex Hospital, Middlesex; Hairmyres Hospital, South Lanarkshire; Christie Hospital, Manchester; Withington Hospital, Manchester; North Manchester General Hospital, Manchester; St James’ University Hospital, Leeds; Harrogate District Hospital, Harrogate; Halifax General Infirmary, Halifax; Castle Hill Hospital, Cottingham; York District Hospital, York; Huddersfield Royal Infirmary, Huddersfield; Bradford Royal Infirmary, Bradford; Airedale General Hospital, Keighley; Leeds General Infirmary, Leeds; Weston Park Hospital, Sheffield; Gwynedd Hospital, Bangor; Velindre Hospital, Cardiff; Singleton Hospital, Swansea; Royal Gwent Hospital, Gwent; Princess Of Wales Hospital, Bridgend; University Hospital of Wales, Cardiff; Frenchay Hospital, Bristol.
The following countries took part in this study:
Argentina, Australia, Belgium, Bosnia, Bulgaria, Croatia, Czech Republic, Denmark, Egypt, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Luxembourg, Malta, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Romania, Russia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, United Kingdom, USA, Yugoslavia.