AFPep, anovel drug for the treatment and prevention of breast cancer: An investigation of potential side effects on the reproductive cycle Free

B131

Full term pregnancy lowers the risk of breast cancer, attributed partly to alpha-fetoprotein (AFP). A small AFP-derived peptide (AFPep) which mimics the active site of AFP has been developed and may be useful for decreasing the risk of breast cancer in women. AFPep has been shown to stop the growth of estrogen dependent human breast cancer xenografts in mice and prevent carcinogen-induced breast cancer rats. Since AFPep acts as an estrogen antagonist, it is important to assess the effects on the female reproductive cycle and fertility. If AFPep does not have any undesirable side effects, it will be more appealing as a preventative treatment in women with a high risk breast cancer. The hypothesis is that AFPep will not affect the estrous cycle or fertility in rats. Ten female Sprague-Dawley rats (age 81 days) were given 100 µg AFPep s.c. daily for 20 days. Another group of ten rats was given 50 µg tamoxifen s.c. daily and a third group received saline only. Vaginal smears were obtained twice per day and stained to assess estrous cycle phase. The females were then introduced into cages containing mature male Sprague-Dawley rats. Treatment continued daily for two weeks or until females showed signs of mating. Pregnant females were allowed to give birth, and pregnancy success was evaluated. AFPep did not have any significant effect on the incidences of any of the estrous cycle phases. Tamoxifen significantly increased the length of diestrus, locking the cycle of most animals in this phase. Half of the tamoxifen treated rats mated, and none of them became pregnant. Nine of ten rats in the AFPep group mated, and eight gave birth. Neither AFPep nor tamoxifen had any significant effect on body mass of treated females. We conclude that tamoxifen affects the estrous cycle to the extent that cycling ceases and causes delayed fertility in female rats. AFPep does not affect the cycle allowing it to continue normally and having no effect on fertility. Thus, AFPep may be an attractive option for breast cancer prevention.