AACR 2020: Can Fasting Enhance Endocrine Therapy in Breast Cancer?
Posted: Thursday, May 7, 2020
According to research presented as part of the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting (Abstract CT075), fasting and fasting-mimicking diets may enhance the effect of endocrine therapy in patients with hormone receptor–positive breast cancer. The study utilized in vitro and in vivo experiments to determine whether such dietary practices delayed the occurrence of treatment resistance.
“Overall, our results provide the rationale for conducting further clinical studies of fasting-based dietary strategies as an adjuvant to [endocrine therapy with or without] CDK4/6 inhibitors in patients with [hormone receptor–positive breast cancer],” concluded Alessio Nencioni, MD, PhD, of the University of Genoa, Italy, in colleagues.
The study relied on several investigative approaches, including the evaluation of hormone receptor–positive breast cancer cell lines MCF7, T47D, and ZR-75-1 and organoids derived from metastases in the in vitro experiments. The in vivo experiments included 6- to 8-week-old female mice xenografted with human breast cancer cell lines. The mice received endocrine therapy either with or without 48 to 72 hours of fasting or fasting-mimicking diets. Tumor growth and overall survival were tracked, and tumor and blood samples both from the mice as well as from 36 patients enrolled in one of two previous trials were used to measure circulating levels of growth factors, adipokines, and cytokines. Additional evaluations of IGF1, insulin, and leptin levels were also performed.
Periodic fasting or fasting-mimicking diets were found to lower circulating IGF1, insulin, leptin levels, and block AKT-mTOR signaling, thereby amplifying the effect of endocrine therapy activity from tamoxifen and fulvestrant. In instances of concurrent fulvestrant and palbociclib, periodic fasting resulted in prolonged tumor regression and weakened acquired resistance. Fasting and fasting-mimicking diets both inhibited endometrial hyperplasia. In both humans and mice, fasting-mimicking diets resulted in a prolonged decrease in levels of leptin and IGF1.
Disclosure: The study authors reported no conflicts of interest.
