Breast cancer is one of the most common
cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu
breast cancer oncogene under the control of an MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent
breast cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet (AIN-76A), has previously been shown to significantly delay the development of
mammary cancer in the TG.NK model. Four-week old hemizygous TG.NK female mice with MMTV/c-neu oncogene were fed NTP-2000 diet containing the
retinoid analogue 4-hydroxyphenyl
retinamide (4-HPR) at 5 mM/kg or an
arotinoid Ro 40-8757 at 2 and 3 mmol/kg for 26 weeks. The
4-HPR at 5 mmol/kg diet delayed the development of palpable
tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet control group. However, the
4-HPR diet markedly decreased the average weight of the
tumors at 26 weeks. The
4-HPR diet also caused a significant increase in
body weight without an increase in food consumption. Arotinoid
Ro-40-8757 at both doses inhibited the development of mammary
tumors for the duration of the study. However, the
Ro 40-8757 at 3 mmol/kg appeared to be toxic as indicated by a significant depression of the average
body weight with
alopecia and skin scaling in some mice. Our observations with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the
arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development of
mammary cancer than
4-HPR. Studies to evaluate genetic changes and expression of hormonal receptors and
growth factors associated with the inhibition of
mammary cancer development by the
retinoid analogues are in progress.