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For hormone receptor–positive breast cancer, up-front therapy with an aromatase inhibitor (AI) is an appealing option in premenopausal women who undergo ovarian suppression. In such women (as well as in postmenopausal women), estrogen is derived primarily from aromatization of steroid precursors in adipose tissue, raising the question of whether body-mass index (BMI) influences endocrine treatment outcomes. In an Austrian trial, 1684 premenopausal women (one third of whom were overweight [BMI, 25.0–29.9 kg/m2] or obese [BMI, ≥30.0]) who had hormone receptor–positive breast cancer received the gonadotropin releasing hormone (GnRH) agonist goserelin for ovarian suppression and were randomized to either tamoxifen or the AI anastrozole.
At median follow-up of 63 months, disease-free survival (as well as overall survival) was similar in the two treatment groups for normal-weight women. However, overweight women who received anastrozole had 49% higher risk for disease recurrence (not statistically significant) and threefold higher risk for breast-cancer–related death (P=0.004) than did those who received tamoxifen.
Pfeiler G et al. Impact of body mass on the efficacy of endocrine therapy in premenopausal patients with breast cancer: An analysis of the prospective ABCSG-12 trial. J Clin Oncol 2011 May 9; [e-pub ahead of print]. (http://dx.doi.org/10.1200/JCO.2010.33.2585)
Comment
The authors hypothesize that conventional doses of AI therapy might not adequately suppress serum estrogen levels in obese women, and also that conventional doses of GnRH therapy might not completely suppress ovarian function in premenopausal obese women. Both of these possibilities point to the need for dose-ranging studies of ovarian suppression combined with AI treatment for obese women with premenopausal hormone receptor–positive breast cancer. In general, high BMI compromises outcomes in women with breast cancer (JW Womens Health Dec 22 2010); therefore, weight loss and physical activity should be encouraged whenever possible.