Obesity and endocrine therapy: Host factors and breast cancer outcome

Obesity is becoming increasingly prevalent and it has been linked to poor breast cancer outcomes. Because obesity is associated with increased adipose tissue mass and aromatase activity [the target of aromatase inhibitors (AIs)], there is concern that these agents may be less effective in women who are overweight or obese. Four of the randomized trials of AIs vs. tamoxifen conducted in the adjuvant breast cancer setting (ATAC, BIG 1-98 and TEAM in the postmenopausal setting and ABCSG-12 in the premenopausal setting) have reported effects of body mass index (BMI) on the relative effectiveness of an AI vs. tamoxifen. Obesity was confirmed as an adverse prognostic factor in ATAC and BIG 1-98 but not the TEAM study; in ABSCG-12, obesity was associated with poor outcomes in the anastrozole arm only. In the three postmenopausal trials, the use of an AI vs. tamoxifen was associated with better outcomes at all levels of BMI [all hazard ratios for recurrence <1, although 95% confidence intervals often included 1 due to lower power and smaller reductions in risk]. Of note, there was no significant interaction of BMI with letrozole (vs. tamoxifen) in the BIG 1-98 trial; while ATAC investigators concluded that the relative benefit of anastrozole (vs. tamoxifen) might be better in thinner (vs. heavier) women. In ABCSG-12, the use of anastrozole (vs. tamoxifen) was associated with significantly worse outcomes in women with BMI ≥25 kg/m2 (similar to the detrimental effect of anastrozole on overall survival seen in the parent trial). These findings do not support the use of BMI as a predictor of AI (vs. tamoxifen) benefit in the adjuvant setting in postmenopausal breast cancer.