Aromatase Inhibitor Estrogen Suppression Related to BMI in Postmenopausal Women with Early ER-Positive Breast Cancer
Anastrozole is believed to be less effective than tamoxifen in women with higher BMI. “This effect with high BMI might hypothetically be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels and might be overcome by the use of an increased dose of anastrozole or, alternatively, the use of a more potent AI such as letrozole,” noted Elizabeth J. Folkerd, PhD, Royal Marsden Hospital, London, UK, and colleagues, in explaining the study's rationale.
They examined plasma estradiol and estrone sulfate levels from a highly sensitive radioimmunoassay available for 44 postmenopausal women who received anastrozole 1mg/day for 3 months followed by letrozole 2.5mg/day for 3 months or the opposite sequence and found that baseline values of estradiol and estrone sulfate were significantly correlated with BMI (P<0.001, and P=0.006, respectively).
Patients receiving treatment had levels of estrogen that were greater at higher BMI levels with both AIs, which was significant with letrozole (P=0.013 estradiol and P=0.035 for and estrone sulfate) but not anastrozole. In fact, letrozole suppressed both estrogen types to a greater extent across all weight groups.
“The differential benefit seen between anastrozole and tamoxifen according to BMI may therefore be a result of at least two factors: differential suppression of estrogen levels by the AI and the variable agonist-antagonist balance seen with tamoxifen according to endogenous estrogen levels,” they wrote.
An accompanying editorial noted, “Limited data suggest that these findings could be clinically relevant, but far more work is needed to determine whether modest differences in degree of estrogen suppression have an impact on the efficacy of the aromatase inhibitors. Until further information is available, these findings should not lead to changes in the choice of hormonal agents for women with early breast cancer.”