Abstract A015: The β-blocker carvedilol prevents DMBA-induced mammary gland tumors

Abstract

Abstract Breast cancer is the most diagnosed cancer globally and is the fifth leading cause of cancer related mortality worldwide. Chemoprevention is a promising method of reducing cancer mortality. However, there are no drugs that are used routinely as breast cancer preventative agents. Carvedilol (CAR), a beta-adrenergic receptor blocker, use in humans reduces breast cancer incidence; therefore, we hypothesized that carvedilol acts as a breast cancer preventative agent. Two protocols were used to evaluate the ability of carvedilol to prevent 15 mg 7,12-Dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. In protocol 1, two doses of carvedilol (2 and 10 mg/kg) were provided as a 7-day pretreatment and throughout the study. In protocol 2, 10 mg/kg tamoxifen and 10 mg/kg carvedilol were provided as a 7-day pretreatment and treatment was halted after six weeks. In all studies carvedilol and tamoxifen were administered in the drinking water, animals were palpated weekly beginning at week 5 to detect the presence and location of mammary tumors, tumors were measured via calipers, and the experiments terminated at week 13. In protocol 1, 10 mg/kg, but not 2 mg/kg carvedilol was effective in delaying the tumor occurrence (P = 0.0002); the first appearance of tumors and median tumor appearance were separated by 6 and 4 weeks, respectively, compared to rats receiving DMBA alone. However, the tumors that appeared, grew at similar rate as those in the DMBA group. In protocol 2, tamoxifen prevented all but 1 rat developing a tumor and was similar to the negative control; however, 10 mg/kg carvedilol was indistinguishable from the DMBA group. Although tamoxifen prevented DMBA-induced breast cancer, the rats drank significantly less water resulting in statistically lower body weight than all other groups. The rats also drank significantly less of the carvedilol-laced water, but not to a degree that affected their body weight. Therefore, continuous carvedilol treatment is essential to achieve the observed chemopreventive effects. Our data demonstrates the chemopreventive activity of carvedilol in a rat model of mammary gland carcinogenesis. The results provide significant implications in breast cancer chemoprevention using carvedilol, which is a safe FDA-approved medicine. Citation Format: Pabitra K. Sardar, Ayaz Shahid, Steven Yeung, Bradley T. Andresen, Ying Huang. The β-blocker carvedilol prevents DMBA-induced mammary gland tumors [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A015.