Aromatase inhibitors such as anastrozole (Arimidex) and letrozole (Femara) are designed to inhibit the action of the enzyme aromatase, which converts androgens into estrogens. Aromatase inhibitors normally are used to treat estrogen receptor positive (ER+) breast cancer in postmenopausal women.
High body mass index (BMI) appears to reduce the effectiveness of aromatase inhibitor treatment, possibly because obesity increases circulating estrogen levels. Now a new study has reported that treatment with letrozole or anastrozole might not adequately suppress levels of circulating estrogen in women with high BMI.
Aromatase inhibitors appear less effective in women with high BMI
As noted above, high BMI has been reported to reduce the effectiveness of treatment with aromatase inhibitors. The authors of one study of anastrozole hypothesized that higher doses or more complete inhibitors might be required for overweight women, but this has not been confirmed. It has also been suggested that tamoxifen might be more appropriate treatment for obese women since tamoxifen interferes with a tumor's ability to use estrogen (whereas aromatase inhibitors block the production of estrogen).
High BMI results in less effective suppression of estrogen production
The study referenced at the beginning of this news article was designed to investigate whether suppression of circulating estrogen (estradiol and estrone sulfate) levels by the aromatase inhibitors anastrozole and letrozole is related to BMI. It has been reported recently that anastrozole has lower effectiveness compared to tamoxifen in women with high BMI. In theory, this might be overcome by using a higher dose of anastrozole or by using a more potent aromatase inhibitor such as letrozole. The study included 44 postmenopausal women with early ER+ breast cancer. Baseline plasma estradiol and estrone sulfate levels were determined. The women were divided into two groups who received anastrozole (1 mg per day) for three months followed by letrozole (2.5 mg per day) for three months or vice versa.
High BMI was found to be associated with elevated baseline levels of both estradiol and estrone sulfate. Both aromatase inhibitors greatly reduced estrogen levels in obese women, however, the women's estrogen levels remained more than twice those of normal weight women. Levels of circulating estrogen were found to be higher at higher BMI levels under both aromatase inhibitor treatments, although this was statistically significant only for letrozole. In fact, suppression of both estradiol and estrone sulfate was greater under letrozole across every level of BMI. The authors conclude that the degree of suppression of estrogen in postmenopausal women with early ER+ breast cancer treated with anastrozole and letrozole is related to BMI.
Please see our articles on endocrine treatment and aromatase inhibitor diet for more information.