Chemopreventive effect of the aromatase inactivator exemestane in the dimethylbenzanthracene (DMBA)-induced mammary tumors in rats

Abstract

3108 Background: Exemestane (E, Aromasin) is an aromatase inactivator indicated for the treatment of advanced breast cancer (BC) and under evaluation for early BC. Methods: We have investigated the chemopreventive effect of E in the DMBA-induced mammary tumor in rats, an estrogen-dependent BC model. Tumors were induced by a single oral dose of DMBA (20 mg/rat). One week later animals were divided in five groups (20–22 animals/group): controls, E given weekly IM as a depot formulation at three dose levels (4, 20 or 100 mg/kg/week for 19 weeks) and ovariectomy (OVX). Control and OVX animals received the correspondent vehicle given IM, weekly for 19 weeks. Animals were palpated for tumor formation every week. Results: The final body weight was unchanged at the two lower E doses and increased by 26% and 21% for E 100 mg/kg/week and OVX, respectively. The results on tumor incidence, multiplicity (mean number of tumor per rat), tumor burden and uterus weight are reported in the Table. At the highest dose of 100 mg/kg/week E markedly reduces tumor incidence, multiplicity and burden at the end of the study period, similarly as effective as OVX. E causes a slight reduction in uterus weight only at the intermediate dose of 20 mg/kg/week. Conclusions: These data indicate that E is an active BC chemopreventive agent in an animal model. A 3-arm chemoprevention study using E +/- celecoxib vs placebo in post-menopausal women at risk is underway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia Italia