The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial

Abstract

Background:We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment.Methods:The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety.Results:In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07).Conclusion:Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.

Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

“…Also the influence of BMI on the extent of E2 deprivation during AI treatment needs further investigation, as it has not been given by weight‐ or body‐surface‐area–related dosing: one standard dosage for all patients. This might explain the worse survival for obese women undergoing endocrine treatment found in several studies …”

Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer

“…Thus, BMI potentially has an impact on the efficacy of AIs to lower estradiol serum levels. Indeed, retrospective analysis of phase III clinical trials demonstrated that overweight and obese patients have a worse disease outcome when treated with anastrozole compared with normal weight patients (Sestak et al , 2010; Pfeiler et al , 2011; Gnant et al , 2013). As this could not be shown for tamoxifen in these trials, BMI might be a predictive parameter regarding endocrine therapy.…”

Targeting the COX-2 Pathway to Improve Therapeutic Response in the Obese Breast Cancer Patient Population

“…In addition, while recurrence-free survival with anastrozole treatment was higher in comparison to tamoxifen, this benefit was lost in the obese cohort [56*]. Another study found that although three extra years of anastrozole treatment decreased normal weight patients’ risk of disease recurrence and death by half, overweight and obese patients did not benefit from this treatment [57]. Furthermore, plasma estradiol and estrone sulfate levels in obese patients remain significantly elevated in comparison to non-obese patients following letrozole treatment [58], suggesting that this reduced response rate is related to suboptimal inhibition of obesity-associated aromatase activity.…”