Breast cancer is a leading cause of death in the US, affecting more than 200,000 women each year. About 80% of these cancers are estrogen receptor positive (ER+). Several therapeutic options exist for ER+ patients, including selective estrogen-receptor modulators (SERMs) such as tamoxifen; however, these drugs are known to have serious side effects. Tolerability has been a major barrier for development of preventative agents. AFPep is a 9-mer cyclized peptide derived from alpha-fetoprotein (AFP), a protein naturally expressed during fetal development. AFPep has been shown to have therapeutic efficacy against ER+ breast cancer. The aim of this project is to assess the safety and efficacy of AFPep as a preventive agent for breast cancer. Preventative efficacy of AFPep was assessed in August Copenhagen Irish (ACI) rats, a strain that develops breast cancer when exposed to high but physiological levels of estrogen. Female rats were exposed to estrogen through subcutaneous estradiol implants for 24 weeks. Rats were treated once daily with saline or 25 µg AFPep for 4 weeks to mimic pregnancy. Tumors were monitored twice weekly for 24 weeks. Tolerability was assessed using animal weight, behavioral parameters, and organ weights at necropsy. AFPep significantly decreased formation of mammary tumors under estrogen exposure and showed no signs of adverse effects after lengthy duration of administration. A comparison of cancer prevention models in rats delineates the advantages and disadvantages of two commonly used approaches.
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