Establishment of novel rat models for premalignant breast disease

Abstract

Background Breast cancer has become one of the most common malignant tumors among females over the past several years. Breast carcinogenesis is a continuous process, which is featured by the normal epithelium progressing to premalignant lesions and then to invasive breast cancer (IBC). Targeting premalignant lesions is an effective strategy to prevent breast cancer. The establishment of animal models is critical to study the mechanisms of breast carcinogenesis, which will facilitate research on breast cancer prevention and drug behaviors. In this study, we established a feasible chemically-induced rat model of premalignant breast cancer. Methods Following the administration of the drugs (carcinogen, estrogen, and progestogen) to Sprague-Dawley (SD) rats, tumors or suspicious tumors were identified by palpation or ultrasound imaging, and were surgically excised for pathological evaluation. A series of four consecutive steps were carried out in order to determine the carcinogen: 7,12-dimethylbenzaanthracene (DMBA) or 1-methyl-1-nitrosourea, the route of carcinogen administration, the administration period of estrogen and progestogen, and the DMBA dosage. Results Stable premalignant lesions can be induced in SD rats on administration of DMBA (15 mg/kg, administered three times) followed by administration of female hormones 5-day cycle. Results were confirmed by ultrasound and palpation. Conclusion Under the premise of drug dose and cycle, DMBA combined with estrogen and progestogen can be used as a SD rat model for breast premalignant lesions.