Abstract 1248: Adult calorie restriction reduces weight gain and mammary tumor incidence in obesity prone MMTV-TFG α mice -
Authors: Michael E. Grossmann, Nancy K. Mizuno, Da-Qing Yang, D. Joshua Liao, Margot P. Cleary
Journal: Cancer Research (2017)

Abstract Obesity is associated with increased risk of postmenopausal breast cancer resulting in recommendations for weight gain prevention and/or weight loss. However, there is little experimental data indicating if calorie restriction (CR) initiated in adulthood impacts mammary tumorigenesis. We have used female MMTV-TGF-α mice which develop mammary tumors in the 2nd yr of life as a model of postmenopausal breast cancer. From 10-30 weeks of age (woa) mice were fed a diet with 33% fat calories. At 30 woa based on body weight mice were classified as Obesity-Prone (Ob-Pr), Overweight (Ow) or Obesity-Resistant (Ob-R). Half in each weight category were then fed a 25% CR diet with reduced carbohydrate content (43% fat calories). The remaining mice continued on ad libitum (AL) feeding of the 33% fat diet. This resulted in six experimental groups (n = 26-31/group). Food intakes were monitored and body weights and mammary tumor status were determined weekly. Mice were sacrificed either at 90 woa or earlier if tumor size dictated. Mice in the CR-Ob-Pr group lost an average of 1.12 grams while mice in the AL-Ob-Pr group gained 16.03 grams from 30 woa until euthanasia. CR-Ob-Pr mice had a reduced palpable tumor incidence as compared to AL-Ob-Pr mice prior to euthanasia (12.90% versus 61.54% P = 0.0002). Indolent tumors were discovered at euthanasia with the CR-Ob-Pr mice having a larger number than AL-Ob-Pr mice resulting in final tumor positive mice in these groups of 54.84% vs 65.38%, respectively. Interestingly, the Ob-R mice had final tumor incidence of 38.71% and 73.08% for the CR-Ob-R vs the AL-Ob-R (P&amp;lt;0.01). Average tumor weight was highest in the AL-Ob-Pr group with CR resulting in a significantly lower tumor weight (P&amp;lt; 0.01). The AL-Ob-Pr group had the shortest average survival time of 82.96 woa while CR of the Ob-Pr mice resulted in increased survival to 89.77 woa (P &amp;lt; 0.001). A comparison of the survival curves of these two groups showed that CR resulted in significantly increased survival (P &amp;lt; 0.0001). Results of this study indicate that initiation of moderate 25% CR during adulthood reduces weight gain, mammary tumor incidence, and tumor weight as well as increases lifespan even when a moderately high fat diet was consumed. This information supports further efforts to be made to prevent weight gain as women approach menopause to delay or prevent breast cancer development. Support: NIH-CA157012, The Hormel Foundation and Paint the Town Pink. Citation Format: Michael E. Grossmann, Nancy K. Mizuno, Da-Qing Yang, D. Joshua Liao, Margot P. Cleary. Adult calorie restriction reduces weight gain and mammary tumor incidence in obesity prone MMTV-TFG α mice - [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 1248. doi:10.1158/1538-7445.AM2017-1248