Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea

Vorozole, a nonsteroidal aromatase inhibitor, impedes the post-initiation s tage of chemically induced mammary carcinogenesis. While various aspects of vorozole's effects on mammary carcinoma development have been investigated , little attention has been directed to determining the estrogen receptor ( ER) and progesterone receptor (PR) content of mammary carcinomas that arise despite vorozole treatment. Female Sprague-Dawley rats were given an i.p. injection of 50 mg MNU/kg body weight at 21 days of age and placed on diet supplemented with 0 or 3 mg vorozole/kg, which had no effect on mammary tum or development. Histologically confirmed carcinomas were evaluated for ER a nd PR by immunohistochemistry. In the control group, 78.8% of carcinomas we re ER positive with an ER content ranging from 13.8 to 40.0%, similar to ER content of mammary ductal epithelial cells from non-carcinogen treated ani mals. PR content ranged from 4.4 to 45.2% and also was similar to levels of PR observed in ductal epithelial cells. ER was not correlated with PR in m ammary carcinomas (r = 0.05, p > 0.80), whereas there was a significant cor relation in ductal epithelium (r = 0.86, p = 0.006). In vorozole-treated ra ts, no ER negative carcinomas were observed and overall ER expression by vo rozole was elevated (p < 0.03). All carcinomas from vorozole-treated rats e xpressed PR (2.5-60.2%) and correlation between ER and PR content was numer ically greater in carcinomas from vorozole-treated animals (r = 0.42, p = 0 .09). These data, which are considered hypothesis generating, provide evide nce that low doses of vorozole in the diet select for mammary carcinomas wi th an increased ER positive phenotype.