Abstract 5321: Metabolomics and body mass index among breast cancer survivors in The Lifestyle, Exercise, and Nutrition (LEAN) Study
Authors: Ferrucci Leah M. , Cartmel Brenda , Harrigan Maura , Sanft Tara , Playdon Mary , Jia Wei , Yu Herbert , Johnson Caroline H. , Pusztai Lajos , Chagpar Anees B. , Irwin Melinda L. 
Published: July 2017

Abstract
Background: While there is a growing body of literature on metabolomics and body mass index (BMI), there are limited studies in relation to weight change in overweight and obese individuals, and to our knowledge, no such studies in breast cancer survivors.
Methods: The Lifestyle, Exercise and Nutrition (LEAN) randomized diet- and exercise-induced weight loss trial in breast cancer survivors enrolled overweight or obese breast cancer survivors (Stage 0-III) identified via the Yale-New Haven Hospital tumor registry or self-referral. Participants were randomized to either usual care group (n=33) or the 6-month lifestyle intervention (11 sessions with a registered dietitian) (n=67). Height and weight were measured by study staff at baseline and 6 months, and a fasting (≥ 12 hours) blood draw was also performed at these time points. Paired (baseline and 6-month) serum metabolomics data were available for 83 women. Only those metabolites consistently detected in &gt;80% of quality control samples with a coefficient of variation &lt;30% were included in data analysis. We evaluated partial Pearson correlations between the ratio of metabolites at baseline versus 6-months and change in BMI adjusted for age and intervention group. We also assessed mean changes in metabolites from baseline to 6-months by randomization group using the general estimating equation in linear regression. Adjustment for multiple comparisons was based on the False Discovery Rate (FDR) with a threshold of 0.1.
Results: Overall, a total of 307 metabolites were analyzed; 168 were quantitated by LC-MS and 139 were semi-quantitated by GC-TOF/MS. For BMI change from baseline to 6-months, we observed correlations with 16 metabolites (isocitric acid, 3-hydroxybutyric acid, serine, L-cysteine, petroselinic acid, aminomalonic acid, palmitoleic acid, linoleic acid, 2-hydroxybutyric acid, and seven unidentified metabolites, p &lt;0.05), however FDR correction for multiple comparisons yielded no statistically significant results. We also observed differences by randomization group for L-alanine, dopamine, serotonin, PCaaC36:1, 3-hydroxyoleoylcarnitine, and PCaeC36:1 in bivariate analyses, but in models adjusted for age and BMI only L-alanine remained significant (p&lt;0.05). After correction for FDR, there were no significant differences by randomization group.
Conclusions: There were no clear associations between metabolites and change in BMI or randomization group among overweight and obese breast cancer survivors enrolled in a weight loss trial. Larger sample sizes would help to clarify if any of the potential signals observed in this population may be associated with BMI or other lifestyle changes, such as diet quality.
Citation Format: Leah M. Ferrucci, Brenda Cartmel, Maura Harrigan, Tara Sanft, Mary Playdon, Wei Jia, Herbert Yu, Caroline H. Johnson, Lajos Pusztai, Anees B. Chagpar, Melinda L. Irwin. Metabolomics and body mass index among breast cancer survivors in The Lifestyle, Exercise, and Nutrition (LEAN) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5321. doi:10.1158/1538-7445.AM2017-5321