Results from a long-term follow up from the Intergroup Exemestane Study’s (IES) data published in the Journal of Clinical Oncology reveals that women’s risk of dying from breast cancer can be reduced by changing to an aromatase inhibitor called exemestane after two to three years of tamoxifen treatment.

The standard treatment for women diagnosed with early stage estrogen receptor-positive (ER+ or hormone sensitive) breast cancer until recently was administration of tamoxifen for about five years after surgery to help prevent recurrence, a therapy that has been shown to lower the risk of mortality by 34%. Recently, more and more women have been treated with aromatase inhibitors either as first-line treatment or after treatment with tamoxifen.

The Intergroup Exemestane Study (IES), a collaborative large-scale trial led by The Institute of Cancer Research’s Clinical Trials & Statistics Unit (ICR-CTSU) and Imperial College London’s Clinical Trials Unit (Cancer) examined the long-term efficacy of switching to exemestane after two to three years tamoxifen to complete a total of five years adjuvant treatment. The trial was conducted across 37 countries in 1998 and funded by Pfizer Inc.

The trial involved random assignment to either continue tamoxifen therapy or change to exemestane for the remainder of the 5-year period in postmenopausal patients who were disease-free after two to three years. According to the results published in 2007 those who switched drugs showed increased survival rates although it was unclear whether this trend would continue in the years following the end of the treatment and whether there would be any long-term side effects.

Findings of the trial published recently include 4,052 patients with ER+ cancer and 547 women with tumors of unknown ER status. The researchers discovered after a median follow-up of 91 months that women whose therapy had been changed to exemestane tended to have an 18% reduced risk of recurrence and a 14% lower mortality risk compared with those who remained on tamoxifen.

Those in the exemestane group reported less gynecological side effects and more musculoskeletal side effects during treatment, however, the difference in long-term side effects between both groups were insignificant.

Lead researcher Professor Judith Bliss, Director of the ICR’s Clinical Trials & Statistics Unit, comments: “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 and Head of Division of Cancer at Imperial College London, Professor Charles Coombes, adds: “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.”

Of 48,000 women diagnosed with breast cancer in the UK every year, approximately 75% suffer from an estrogen receptor positive tumor, which involves the hormone estrogen. Although both tamoxifen and exemestane are hormone treatments, tamoxifen blocks a tumor’s ability to use estrogen whilst aromatase inhibitors reduce the production of estrogen in the body.

The researchers hypothesize that some cancer cells can become resistant to the drug during tamoxifen treatment and that exemestane can subsequently kill these resistant cells by withdrawing the estrogen from circulation.

Dr Lesley Walker, Cancer Research UK’s director of cancer information, concludes: “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.”

Written by: Petra Rattue