Impact of BMI on Response to Endocrine Therapy

Study Design: A retrospective analysis of data from a prospective trial of premenopausal women. The original data came from the Austrian Breast and Colorectal Cancer Study Group 12 (ABCSG-12). This study compared the endocrine treatment of goserelin with tamoxifen versus anastrozole in premenopausal patients with endocrine-responsive breast cancer.

Study Eligibility: Premenopausal women with hormone-receptor-positive (estrogen-receptor and/or progesterone receptor positive) early breast cancer from the ABCSG-12 trial. Out of the original 1,803 patients in the ABCSG-12 study, researchers eliminated a total of 52 patients who were underweight.

Enrollment: 1,684 total premenopausal women with early breast cancer, two-thirds were normal weight (n=1,111) and one-third were overweight (n=391) or obese (n=182). BMI measures were as follows: normal = 18.5 to 24.9 kg/m2, overweight = 25 to 29.9 kg/m2, and obese ≥ 30 kg/m2.

Research Question: What is the influence of BMI on the efficacy of adjuvant endocrine therapy in premenopausal patients?

Researchers investigated the influence of body mass index (BMI) on the efficacy of adjuvant endocrine therapy in premenopausal patients in a retrospective analysis of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 trial. Previous studies have found that overweight women have higher levels of the aromatase enzyme. The researchers were investigating the possibility that increased BMI may negatively influence the efficacy of aromatase inhibitors to block aromatase and lower serum estrogen levels.

The researchers used data from the ABCSG-12 study that examined the efficacy of ovarian suppression, using goserelin, in combination with anastrozole (an aromatase inhibitor) or tamoxifen, with the primary endpoint being disease-free survival (DFS). The BMI categories were as follows: normal = 18.5 to 24.9 kg/m2, overweight = 25 to 29.9 kg/m2, and obese ≥ 30 kg/m2. Data were analyzed for DFS and overall survival (OS) according to the BMI subgroups and the two treatment arms (goserelin combined with either tamoxifen or anastrozole).

Overweight patients were found to have decreased DFS and OS compared to normal weight patients (HR=1.24; 95% Cl, 0.60 to 1.64; P =.15). Among patients treated with tamoxifen, there were no differences in DFS or OS between normal and overweight patients. However, in the anastrozole treatment arm, overweight patients had a statistically significant increase in the risk of recurrence compared to normal weight patients, 15.1% vs. 9% respectively (P = .01), which translates to a relative risk increase of 60%. When looking at OS, overweight patients treated with anastrozole had more than double the risk of death compared to normal weight patients. Furthermore, within the overweight group, patients treated with anastrozole had an almost 50% increase in the risk of disease recurrence (HR=1.49; 95% CI, 0.93 to 2.38; P = .08) and a three-fold increase in the risk of death (HR=3.03; 95% CI, 1.35 to 6.82; P = .004) compared with patients treated with tamoxifen. However, for normal weight patients, there was no difference in DFS or OS between the tamoxifen and anastrozole groups.

This study suggests that BMI significantly influences the efficacy of anastrozole + goserelin in premenopausal patients with hormone-receptor-positive breast cancer. This most likely occurs through a mechanism of influencing aromatase availability and/or ovarian suppression by goserelin. BMI may also be a useful surrogate parameter for total-body aromatization and even a possible tool to tailor AI therapy for individual patients. Because overweight patients treated with anastrozole did not respond as favorably as those given tamoxifen, it is possible that anastrozole was not able to suppress estrogen serum levels to the same extent as in normal weight patients. It is possible that this problem might be overcome with an increased dose of AIs.

There are a few confounding factors in this study. Overweight patients may have a worse prognosis due to an initially larger tumor size, or altered endocrine functions of fat tissues, as well as comorbidities. Furthermore, although differences were not found in tamoxifen treatment groups in normal or overweight patients, according to an analysis done by the Danish Breast Cancer Cooperative Group, these differences may appear after 5 years of follow-up. More studies are needed to investigate incomplete aromatase inhibition and incomplete ovarian suppression in overweight premenopausal patients. The authors assert that their results should be viewed as hypothesis generating, and a possible consideration of physicians in risk-benefit assessment of adjuvant endocrine treatment for overweight premenopausal women.

Citations

Pfeilger G, Königsberg R, Fesl C, et al. Impact of Body Mass Index on the Efficacy of Endocrine Therapy in Premenopausal Patients With Breast Cancer: An Analysis of the Prospective ABCSG-12 Trial. JCO. 2011 May 9: JCO.2010.33.2585; published online on May 9, 2011

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