PROGESTERONE INDUCTION OF MAMMARY CARCINOMAS IN BALB C FEMALE MICE - CORRELATION BETWEEN PROGESTIN DEPENDENCE AND MORPHOLOGY/

We have demonstrated that medroxyprogesterone acetate (MPA), when admi nistered in high doses, induces mammary carcinomas in virgin female BA LB/c mice. Since one of the possible explanations for this effect was its progestagenic effects, we decided to investigate whether progester one (Pg) alone could also induce mammary adenocarcinomas in our model and if MPA at doses lower than those used to establish the model was a lso carcinogenic. A total of 136 mice were subdivided info 3 groups: G roup 1, 44 mice were implanted s.c. with 40 mg Pg silastic pellets at the beginning of the experiment, and 6 months later with a 20 mg Pg pe llet; Group 2, 45 mice were similarly treated with MPA pellets; Group 3, 47 mice were inoculated s.c. with 40 mg MPA every three months. At the end of 20 months, 9 animals had developed mammary tumors in Group 1, 18 in Group 2 and 34 in Group 3 (actuarial incidence = 28%, 58%, an d 98%, respectively); tumor latency was similar in all groups: 46.2 +/ - 13.1, 51.3 +/- 9.9, and 50.1 +/- 2.1 weeks, respectively. Seven (Gro up 1),14 (Group 2), and 25 (Group 3) tumors were transplanted into syn geneic mice to determine progestin dependence. All tumors, except one from Group 1, were histologically characterized. In Group 1 (Pg 60 mg) , 4 tumors (67%) were infiltrating lobular carcinomas and 2 were ducta l carcinomas (33%). In Group 2 (MPA 60 mg), 2 tumors (14%) were lobula r and 12 were ductal adenocarcinomas (86%) (Group 1 vs Group 2: p < 0. 05), whereas in Group 3 (MPA 160 mg), 8 were lobular carcinomas (32%) and 17 were ductal carcinomas (68%). In syngeneic passages all lobular tumors behaved as progestin independent (PI) and ductal tumors as pro gestin dependent (PD). All ductal tumors, except one, expressed estrog en receptors (ER) and progesterone receptors (PR), whereas receptor ex pression was variable in lobular carcinomas. It can be concluded that Pg induces mostly lobular, PI mammary tumors in BALB/c female mice. Th e fact that most MPA-induced tumors are ductal and PD suggests that th e two hormones use different carcinogenic pathways.