The MA-17 Trial.
This placebo-controlled trial investigated whether postmenopausal women with hormone-receptor-positive tumors, who have completed five years of tamoxifen therapy, would benefit from further treatment with letrozole ("Femara"). This trial shows a reduction of breast cancer events from 5.9% in the placebo arm to 2.9% in the letrozole arm at a median follow-up time of 2.4 years. This translates to about 1 event per 100 women treated per year. This trial also shows a small benefit in overall survival but only in women whose lymph nodes were involved at the time of surgery. Further data on long-term effects will be confused, however. The reason is that the trial organizers felt that the trial should be closed to allow women on the placebo arm to take letrozole if they wished to. Long term data on the original target of the trial, which was to have been five years of letrozole treatment, will now never be known.
Aromatase Inhibitors after tamoxifen - the Italian Experience
At the San Antonio Breast Cancer Symposium in December 2003, the results were presented of an Italian study in which 448 women were randomly assigned either to continue their tamoxifen after the second year, or to switch a that point to the aromatase inhibitor, Arimidex. The patients were treated between 1998 and 2002 so the median time of follow-up is quite short at just 2 years. However, these preliminary results show that women who switched treatment had around half as many recurrences and new breast cancers.
The Intergroup Exemestane Study
In this study, published in the New England Journal of Medicine in March, 2004, 4742 postmenopausal women who had undergone excision of primary breast cancer and were then treated with tamoxifen for two to three years were randomized to either continue the tamoxifen, or switch to exemestane ("Aromasin").
The group of women who had been assigned to switch to the aromatase inactivator
exemestane had significantly longer disease free survival than women who continued to receive tamoxifen. This means that those on exemestane had fewer recurrences and fewer new primary breast cancers, but as yet there is no evidence that they LIVE longer ("overall survival").
Again this trial is supporting the fact that the aromatase inhibitors appear to be superior to tamoxifen in preventing breast cancer recurrence when used as adjuvant treatment in women who have passed the menopause.

This study involves more than 8000 postmenopausal women (800 in Australia and New Zealand) with early, hormone-sensitive breast cancer and is testing the following five year treatment plans:
1) five years of tamoxifen alone versus five years of letrozole ("Femara") alone; 2) the sequence of tamoxifen for two years followed by letrozole for three years; 3) the sequence of letrozole for two years followed by tamoxifen for three years.
Among the 4003 patients in the letrozole group, 84.0% remained alive and disease-free at five years compared with 81.4% of the 4007 patients in the tamoxifen group. The reduction in rates of recurrence was seen for both local (breast) recurrences and distant recurrences. Tamoxifen was associated with more venous thrombosis and embolism (clots), and more vaginal bleeding, leading to more endometrial abnormalities (changes in the lining of the womb) and endometrial biopsies. Letrozole was associated with more bone fractures, elevation of cholesterol (though this was usually mild) and more heart attacks and strokes, though these events were very rare with both treatments.
Professor Richard Gelber of Harvard Medical School and Statistician for the trial said, "The first results of BIG 1-98 demonstrate clear superiority of letrozole compared with tamoxifen to reduce the risk of breast cancer recurrence (especially in distant metastatic sites) for postmenopausal women following surgery for breast cancer which contains hormone receptors in the tumor cells.
The two drugs are well tolerated, but letrozole therapy compared with tamoxifen is associated with increased risks of bone fractures, hypercholesterolemia, and deaths without breast cancer recurrence due to cerebrovascular accident or cardiac causes. This finding, which is not associated with compromised overall survival, requires additional attention, because previous studies of the cardiovascular risk of the aromatase inhibitors have not focused properly on this aspect. Until additional information becomes available, aromatase inhibitors should be used with caution, especially in patients at elevated risk for cardiovascular disease."