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Aclass of hormonal drugs called aromatase inhibitors substantially reduce therisk of death in postmenopausal women with the most common type of breastcancer, a major study of more than 30,000 women shows.
Theresearch underlines the importance of aromatase inhibitors in the treatment ofoestrogen receptor (ER)-positive breast cancer – and shows they reduce risk ofdeath by significantly more than the older hormonal treatment tamoxifen.
Thestudy, published in The Lancet, is relevant to postmenopausalwomen with ER-positive breast cancer, which accounts for over 80 per cent ofcases which occur after the menopause. Each trial had used both aromataseinhibitors and tamoxifen at various times during the course of treatment.
Inthe study, researchers from the Aromatase Inhibitors Overview Group – chairedby Professor Mitch Dowsett at The Institute of Cancer Research, London and TheRoyal Marsden NHS Foundation Trust – collaborated with colleagues at theClinical Trials Service Unit at The University of Oxford, to combine theresults from 31,920 women in nine clinical trials.
Thestudy was funded by Cancer Research UK and the Medical Research Council andconducted under the umbrella of the Early Breast Cancer Trialists CollaborativeGroup.
Aromataseinhibitors suppress the synthesis of oestrogens and are taken by postmenopausalwomen with hormone-sensitive (ER-positive) breast cancer. They have previouslybeen reported to reduce the risk of recurrence more effectively than tamoxifen,but improvements in survival had not been demonstrated.
Thecurrent study showed that taking aromatase inhibitors for five years reducedthe risk of postmenopausal women with ER positive breast cancer dying of theirdisease by 40 per cent within 10 years of starting treatment, compared with nohormonal treatment. Thiscompares with the 30 per cent reduction achieved by taking tamoxifen for fiveyears.
Currentclinical guidelines reflect the uncertainty in when to use aromatase inhibitorsor tamoxifen in the course of treatment – but the new study could help clarifythese recommendations.
Studylead author Professor Mitch Dowsett, Head of the Academic Department ofBiochemistry and of the Centre for Molecular Pathology at The Royal Marsden andThe Institute of Cancer Research, London, said: “Ourglobal collaboration has revealed that the risk of postmenopausal women withthe most common form of breast cancer dying of their disease is reduced by 40per cent by taking five years of an aromatase inhibitor – a significantlygreater protection than that offered by tamoxifen. Aromataseinhibitors remove only the tiny amount of oestrogen that remains in thecirculation of women after the menopause – but that’s enough to have asubstantial impact on a wide range of ER-positive tumours, despite theirextraordinary differences at the molecular level. Butaromatase inhibitor treatment is not free of side-effects, and it’s importantto ensure that women with significant side-effects are supported to try tocontinue to take treatment and fully benefit from it.”
ProfessorPaul Workman, Chief Executive of The Institute of Cancer Research, London,said: “The evidence on aromatase inhibitors has been accumulating for well overa decade, but it has taken this huge and complex study to make sense of all thedata, and provide a firm basis for clinical guidelines. “Ittends to be the discovery of new treatments that grabs the headlines, but it isjust as important to maximise the benefit patients get from existingtreatments, through major, practice-changing studies like this.”
Thestudy is published in The Lancet alongside another major breast cancerstudy of a different drug type – called bisphosphonates – led by researchers atOxford and the University of Sheffield and also funded by Cancer Research UKand the Medical Research Council.
The Instituteof Cancer Research (ICR) and The Royal Marsden played a leading role in earlieras well as the current clinical trials that demonstrated the effectiveness ofaromatase inhibitors in breast cancer, and in identifying and validatingbiomarkers to determine who could benefit. These studies supported therecommendation by NICE that the drugs should be first-line hormone treatmentfor certain women after surgery.
Thestudy follows on from another recent study led by Professor Dowsett whichindicated that women with high levels of the oestrogen receptor might benefitfrom extended treatment with hormone therapy – which usually stops after fiveyears.