Abstract P3-08-01: Randomized controlled trial of weight loss vs. usual care on telomere length in women with breast cancer: The lifestyle, exercise and nutrition (LEAN) study
Authors: Sanft T , Lu L , Harrigan M , Cartmel B , Zhou Y , Chagpar A , Pusztai L , Irwin M 
Published: May 2016

PURPOSE: Some studies suggest that telomere shortening due to repeated cell divisions may be associated with increased breast cancer risk and mortality. Obesity is also associated with increased breast cancer risk and mortality. Few studies have examined telomere length as a potential mechanism/biomarker mediating the obesity-breast cancer association. One study published of a diet, physical activity and support intervention in prostate cancer patients found a positive association between lifestyle changes and relative lengthening of telomeres, and another study of weight loss in healthy postmenopausal women observed no effect of weight loss on leukocyte telomere length. The purpose of our study was to examine the effect of a 6-month diet- and exercise-induced weight loss intervention vs. usual care on telomere length in 100 breast cancer survivors.

METHODS: 100 breast cancer survivors with BMI≥25 kg/m2 were randomly assigned to a weight loss counseling intervention with either telephone or in-person counseling (n = 67) or usual care group (n=33). Weight loss counseling included eleven 30-minute counseling sessions over 6 months, focusing on reducing caloric intake, increasing physical activity and behavioral therapy. Body composition (height, weight, and DEXA scans), physical activity and diet were measured at baseline and 6-months. Fasting blood samples were also collected at baseline and 6 months. Relative telomere length (T/S: telomere length/single copy of gene albumin) was measured by quantitative-polymerase chain reaction (qPCR) done on buffy coat extracted genomic DNA. Mean baseline to 6-month changes were compared between groups (intent-to-treat) using generalized estimating equations and Pearson correlation coefficients.

RESULTS: Baseline characteristics were similar for women randomized to each group. Women were 59±7 years, with BMI 33.1±6.6 kg/m2 and were 2.9±2.1 years from diagnosis; 91% were non-Hispanic white, and 51% were diagnosed with Stage I breast cancer. Average 6-month weight loss was 6.2% and 2.0% for weight loss and usual care groups, respectively (p=0.0004). At baseline, higher % body fat was associated with shorter T/S (r = -0.31, P=0.012). After 6 months, women randomized to weight loss experienced a 4% T/S lengthening compared to a 5% T/S shortening in the usual care group (P=0.10) (Table 1).

Effect of weight loss vs. usual care on leukocyte telomere lengthLEAN VariableUsual Care  Weight Loss Group  TelomereNMeanSDNMeanSDBaseline330.850.26630.750.216 Month Change26-0.040.21540.030.18  (-5%)  (+4%)p=.10SD=Standard Deviation

CONCLUSION: Our results indicate that higher % body fat is associated with shorter leukocyte telomere length, and weight loss was associated with an increase in leukocyte telomere length, suggesting that telomere length may be a mechanism mediating the relationship between obesity and breast cancer risk and mortality.

Citation Format: Sanft T, Lu L, Harrigan M, Cartmel B, Zhou Y, Chagpar A, Pusztai L, Irwin M. Randomized controlled trial of weight loss vs. usual care on telomere length in women with breast cancer: The lifestyle, exercise and nutrition (LEAN) study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-08-01.