Prevention of rat mammary carcinoma utilizing leuprolide as an equivalent to oophorectomy

A clinical trial is currently under way to examine the effectiveness of leu prolide as a breast cancer chemopreventive agent and contraceptive. This tr ial, as well as similar proposed studies, is based on the assumption that l euprolide is as effective as surgical castration in preventing the onset of mammary tumors; however, this has not been well documented in the DMBA ani mal model. We directly compared leuprolide and oophorectomy in this model a nd examined a combined therapy of leuprolide/bromocriptine. Twenty-seven da y old female Sprague-Dawley rats were randomly allocated into one of eight groups. All rats received a 20-mg dose of DMBA at the age of 55 days. Group 1 (n=10), no treatment; Group 2 (n=9), leuprolide (100 mu g/kg/day) for ei ght weeks beginning four weeks prior to DMBA; Group 3 (n=10), oophorectomy four weeks prior to DMBA with replacement estrogen beginning four weeks fol lowing DMBA. Estrogen replacement was achieved with a 0.05-mg estradiol tab let releasing 0.833 mu g/day over a 60-day period. Group 4 (n=10), leuproli de (100 mu g/kg/day) initiated two weeks prior to DMBA and continuing for t wo weeks following DMBA; Group 5 (n=9), oophorectomy two weeks prior to DMB A with 0.05 mg of estradiol in depot form, releasing 0.833 mu g/day, beginn ing four weeks following DMBA and continuing until week 16 of the study; Gr oup 6 (n=10), leuprolide (100 mu g/kg/day) beginning two weeks prior to DMB A and continuing for the duration of the experiment; Group 7 (n=10), leupro lide (100 mu g/kg/day) for eight weeks beginning two weeks prior to DMBA; G roup 8 (n=9), leuprolide (100 mu g/kg/day) and bromocriptine (83 mu g/day) for eight weeks beginning two weeks prior to DMBA. At nineteen weeks (15 we eks post DMBA), animals were sacrificed and autopsies performed. One hundre d percent of untreated animals developed tumors. No animals undergoing ooph orectomy four weeks prior to DMBA or receiving leuprolide four weeks prior to and simultaneously with DMBA developed tumors. In animals pretreated two weeks prior to DMBA with leuprolide or oophorectomy, each group had one an imal with tumor development. No tumors developed in the animals receiving o ngoing injections of leuprolide. However, one tumor developed in those rece iving leuprolide for the first eight weeks beginning two weeks prior to DMB A administration. One animal receiving both leuprolide and bromocriptine de veloped one tumor. We conclude that chemical oophorectomy (with leuprolide) is as effective as surgical oophorectomy in inhibiting DMBA induced carcin ogenesis.