Effect of body fat mass ratio on prognosis in early stage breast cancer patients using adjuvant aromatase inhibitors

Introduction: Obesity is a risk factor for postmenopausal breast cancer development and a poor prognostic factor for breast cancer. Aromatase inhibitors are used with LHRH analogues, predominantly in postmenopausal period as well as in premenopausal patients. The efficacy data are proven in many studies. However, recent studies suggest that aromatase inhibitors may be less effective in obese patients and this may be related to increased aromatase enzyme activity in the peripheral fat tissue. In obese patients, resistance to aromatase inhibitors and lower survival rate has been shown. The aim of this study is to investigate the role of body fat mass ratio in developing resistance to aromatase inhibitors in breast cancer patients and its efficacy comparison with VKI on lower survival rates. Materials and Methods: We studied 222 patients who had an early stage breast cancer diagnosis between January 2001 and March 2017 and treated with adjuvant aromatase inhibitor treatment with age greater than 18 years. All patients body fat mass ratio were assessed by Tanita. Postmenopausal patients (n=192) were also analyzed. Patients' demographic characteristics, body fat mass ratio, body surface area, body mass index were recorded from patient files. Patients were analysed for body fat mass ratio (FAT%) and body mass index (BMI). The time from diagnosis to relapse was accepted as disease free survival (HSC). Findings: All patients were found to have an average height of 157 ±6,432 cm, a mean weight of 78 ±14 kg, a median body surface area of 1.78 (1,32-2,16) and a mean BMI of 30,9 ±5,89. Mean body fat mass ratio of patients, which were assessed by Tanita device (FAT%), was 39.9 ±6.94, and mean of body fat-free mass of patients was 60,1 ± 6,89. When patients were analyzed in two groups according to BMI <30 and BMI ≥30 (p=0.873), there was no statistically significant difference between the two groups. The disease-free survival data were evaluated by randomizing the patients according to fat mass ratio lower and higher than (45%). There was a statistically significant difference between the two groups (p=0.015). In multivariate analysis, age, grade and fatmass variables were independent predictors of disease-free survival (Fat mass ; <45 and ≥45, OR (odds ratio): 3,511, 95% CI: 1,568-7,865 ; p=0.002, grade [OR: 2,124, 95% CI: 1,140-3,955, age [<50 and > 50, OR: 0.942, 95% CI = 0.912-0.973, p <0.001]) 192 of our patients (86.5%) were postmenopausal. The mean age at the time of diagnosis of postmenopausal patients was 59 (42-91) years. In postmenopausal patients, the average height was 157 ±6,71 cm, the median weight was 78,6 ±13,6 kg, the median body surface area was 1.78 (1.32-2.16) and the mean BMI was 30.9 ±5, respectively. According to the parameters assessed by Tanita device (FAT%), mean fat mass ratio was 40.1 ±6.65, and average ratio of body fat-free mass of patients was detected 59.9 ±6.59. We separated and analyzed postmenopausal patients in two groups according to BMI (Body Mass Index) <30 and ≥30 . There was no statistically significant difference between the two groups (p=0.936). Disease-free survival data were evaluated by categorizing our postmenopausal patients as fat mass ratio lower and higher than 45 %. There was a statistically significant difference between the two groups (p=0.037). In multivariate analysis, fat mass variant was found to be the only independent prognostic factor that significantly affected disease-free survival. (fat- mass ; <45 and ≥45, OR (odds ratio): 3,157, 95% CI: 1,234-8,078, p=0.016). Discussion and conclusion: In the literature, there is no study evaluating the direct effect of body fat mass ratio on disease-free survival and prognosis in patients with breast cancer. All studies in the literature demonstrating resistance to aromatase inhibitors in postmenopausal early stage breast cancer patients were done with body mass index (BMI). Additionally there is no study evaluating the association of body fat mass ratio (fatmass) with aromatase inhibitors resistance. Our study was the first study showing that body fat mass ratio (fatmass) is more successful than body mass index (BMI) in predicting resistance to aromatase inhibitors. Keywords: Breast cancer, Aromatase inhibitors, Body fat mass ratio