A new meta-analysis of previous studies has reported that the cumulative toxicity of aromatase inhibitors when used as treatment for five years may explain the lack of overall survival benefit compared to tamoxifen despite the fact that aromatase inhibitors result in better breast cancer-free survival than tamoxifen. Aromatase inhibitors such as Arimidex (anastrozole), Femara (letrozole), and Aromasin (exemestane) suppress the production of estrogen from androgens within the body whereas tamoxifen blocks estrogen receptors.
The authors performed a systematic search of the MEDLINE and EMBASE databases, as well as databases of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium, to identify trials that compared aromatase inhibitors and tamoxifen as primary anti-estrogen treatment in postmenopausal women. Seven trials with a total of 30,023 patients were selected. The analysis focused on serious side effects, including cardiovascular disease, cerebrovascular disease (mainly stroke), bone fractures, thromboembolic events (blood clots), endometrial cancer (uterine cancer) and other new cancers (not including new breast cancer).
Longer duration of aromatase inhibitor use was found to be associated with increased risk of developing bone fractures and cardiovascular disease, but a lower risk of uterine cancer and blood clots. This conforms to previous findings that tamoxifen increases the risk of uterine cancer and blood clots. Five years of treatment with aromatase inhibitors was associated with a tendency toward increased risk of non-breast cancer specific death compared to five years of tamoxifen alone or tamoxifen for two to three years followed by an aromatase inhibitor for two to three years, but this result was not statistically significant. The authors conclude that the cumulative toxicity of aromatase inhibitors when used as up-front treatment may explain the lack of overall survival benefit compared to tamoxifen despite improvements in breast cancer-free survival. Switching from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the best balance between efficacy and toxicity, according to the authors.