Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: An exploratory analysis from the ATAC trial

Purpose: Third-generation aromatase inhibitors have been widely used in postmenopausal women for the adjuvant treatment of hormone receptor-positive breast cancer. As aromatase inhibitors work by inhibiting the conversion of androgens to estrogens in adipose tissue, we hypothesized that anastrozole may be more effective in women with a high body mass index (BMI). Patients and Methods: The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized clinical trial in which postmenopausal women with early-stage breast cancer were randomly assigned to receive oral daily anastrozole (1 mg) alone, tamoxifen (20 mg) alone, or the combination in a double-blind fashion. Analyses were based on the 100-month median follow-up for women with hormone receptor-positive breast cancers (estrogen [ER] and/or progesterone [PgR] positive). Here, we investigate the impact of BMI on recurrence and the relative benefit of anastrozole versus tamoxifen according to baseline BMI. Results: Overall, women with a high BMI (BMI > 35 kg/m ²) at baseline had more recurrences than those women with a low BMI (BMI < 23 kg/m²; adjusted hazard ratio [HR], 1.39; 95% CI, 1.06 to 1.82; P_{heterogeneity} = .03) and significantly more distant recurrences (adjusted HR, 1.46; 95% CI, 1.07 to 1.61; P_{heterogeneity} = .01). Overall, the relative benefit of anastrozole versus tamoxifen was nonsignificantly better in thin women compared to overweight women. Conclusion: These results confirm the poorer prognosis of obese women with early-stage breast cancer. Recurrence rates were lower for anastrozole than tamoxifen for all BMI quintiles. Our results suggest that the relative efficacy of anastrozole compared to tamoxifen is greater in thin postmenopausal women and higher doses or more complete inhibitors might be more effective in overweight women, but this requires independent confirmation.