A new study has reported that women with high body mass index (BMI) appear to benefit less from hormonal treatments than thin women. Aromatase inhibitors such as Arimidex (anastrozole) are widely used in postmenopausal women for the treatment of hormone receptor positive breast cancer (estrogen positive (ER+) and/or progesterone positive (PR+)). The authors hypothesized that Arimidex may be more effective in women with high BMI since aromatase inhibitors inhibit the conversion of androgens to estrogens in fat tissue.
The study included participants in the Arimidex, Tamoxifen Alone or in Combination (ATAC) study, a double-blind randomized clinical trial in which postmenopausal women with early-stage breast cancer received either Arimidex, tamoxifen, or a combination of the two. The median follow-up period was 100 months. BMI was measured at baseline; high BMI was defined as BMI > 35 kg/m2 whereas low BMI was defined as BMI < 23 kg/m2. In the current study, the impact of BMI on recurrence and the relative benefit of Arimidex compared to tamoxifen according to BMI at baseline were assessed.
Women with high baseline BMI were found to have 39% more recurrences overall than women with low BMI, as well as 46% more distant recurrences. Recurrence rates were lower for Arimidex than tamoxifen for all levels of BMI. In a result that did not support the authors' hypothesis, Arimidex was found to have slightly better outcomes in thin women than in overweight women. The results confirm the previously reported poorer prognosis of obese women with early-stage breast cancer. The authors conclude that the relative efficacy of Arimidex compared to tamoxifen is greater in thin postmenopausal women. Therefore, they speculate that higher doses or more complete inhibitors might be needed in overweight women.
In a related editorial, the editorial writer notes that other obesity-associated factors such as high circulating insulin and insulin resistance may also influence breast cancer growth and prognosis independent of estrogen (and may also interact with estrogen in a way that promotes breast cancer). Therefore, even complete suppression of aromatase might not fully eliminate the poorer prognosis of obese breast cancer patients. One potential approach would be to use metformin, an insulin-lowering agent, to improve breast cancer outcomes in women with high BMI.