Efficacy of tamoxifen±aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial

Abstract

Background:There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.Methods:ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5–24.9 kg m−2), overweight (BMI=25–29.9 kg m−2), and obese (30 kg m−2) according to WHO criteria.Results:Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients.Conclusion:BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.

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

“…In this reanalysis, we did not observe any impact of BMI on the frequency of side effects, which is in line with previous reports (Pfeiler et al , 2011, 2013). Overweight patients had the same frequency of side effects as normal weight patients regarding long-term endocrine therapy with anastrozole.…”

“…For the analyses, we combined overweight and obese patients. As previously shown, the prognostic and predictive impact of BMI is more distinct in obese than in overweight (Sestak et al , 2010; Kwan et al , 2012; Pfeiler et al , 2013). We can therefore not completely exclude that the data presented here are mainly driven by the group of obese patients, and further differentiation between limited weight excess and severe obesity is beyond numerical reason in our trial.…”

The Association Between Adiposity and Breast Cancer Recurrence and Survival: A Review of the Recent Literature

“…[25] A secondary analysis on 1509 patients found that overweight women had poorer distant-recurrence-free survival compared to normal weight women (HR 1.54; 95%CI 1.00–2.35) and obese women had poorer disease-free survival (HR 1.45; 95%CI 1.03–2.02), distant recurrence-free survival (HR 1.79; 95%CI 1.11–2.87 and overall survival (HR 1.82; 95%CI 1.12–2.91) compared to normal weight women. [26] Obese women in the tamoxifen + AI group also had worse disease-free survival (HR 1.78; 95%CI 1.12–2.83), distant recurrence-free survival (HR 2.43; 95%CI 1.25–4.70) and overall survival (HR 2.28; 95%CI 1.16–4.51) compared to normal weight women receiving tamoxifen + AI. No differences across BMI were detected in the tamoxifen only group [26]…”

“…[26] Obese women in the tamoxifen + AI group also had worse disease-free survival (HR 1.78; 95%CI 1.12–2.83), distant recurrence-free survival (HR 2.43; 95%CI 1.25–4.70) and overall survival (HR 2.28; 95%CI 1.16–4.51) compared to normal weight women receiving tamoxifen + AI. No differences across BMI were detected in the tamoxifen only group [26]…”

Targeting breast cancer through its microenvironment: Current status of preclinical and clinical research in finding relevant targets

“…1B.3). Studies comparing treatment efficacy of estrogen targeting between obese and normal weight patients showed contradicting results (Ewertz et al, 2011;Pfeiler et al, 2013). As can be expected, ER positive tumor cells can indirectly be influenced by oophorectomy.…”