Carvedilol blocks neural regulation of breast cancer progression in vivo and is associated with reduced breast cancer mortality in patients

Gillis, Ryan D.; Botteri, Edoardo; Chang, Aeson; Ziegler, Alexandra I.; Chung, Ni Chun; Pon, Cindy K.; Shackleford, David M.; Andreassen, Bettina K.; Halls, Michelle L.; Baker, Jillian G.; Sloan, Erica K.

Abstract

© 2021 Elsevier Ltd
Purpose: The sympathetic nervous system drives breast cancer progression through β-adrenergic receptor signalling. This discovery has led to the consideration of cardiac β-blocker drugs as novel strategies for anticancer therapies. Carvedilol is a β-blocker used in the management of cardiovascular disorders, anxiety, migraine and chemotherapy-induced cardiotoxicity. However, little is known about how carvedilol affects cancer-related outcomes.

Methods: To address this, we investigated the effects of carvedilol on breast cancer cell lines, in mouse models of breast cancer and in a large cohort of patients with breast cancer (n = 4014).

Results: Treatment with carvedilol blocked the effects of sympathetic nervous system activation, reducing primary tumour growth and metastasis in a mouse model of breast cancer and preventing invasion by breast cancer cell lines. A retrospective analysis found that women using carvedilol at breast cancer diagnosis (n = 136) had reduced breast cancer-specific mortality compared with women who did not (n = 3878) (5-year cumulative incidence of breast cancer deaths: 3.1% versus 5.7%; p = 0.024 and 0.076 from univariate and multivariable analyses, respectively) after a median follow-up of 5.5 years.

Conclusions: These findings provide a rationale to further explore the use of the β-blocker carvedilol as a novel strategy to slow cancer progression.

Citation

Gillis, R. D., Botteri, E., Chang, A., Ziegler, A. I., Chung, N. C., Pon, C. K., Shackleford, D. M., Andreassen, B. K., Halls, M. L., Baker, J. G., & Sloan, E. K. (2021). Carvedilol blocks neural regulation of breast cancer progression in vivo and is associated with reduced breast cancer mortality in patients. European Journal of Cancer, 147, 106-116. https://doi.org/10.1016/j.ejca.2021.01.029

• Journal Article Type: Article
• Acceptance Date: Jan 24, 2021
• Online Publication Date: Feb 24, 2021
• Publication Date: Apr 1, 2021
• Deposit Date: Mar 12, 2021
• Publicly Available Date: Feb 25, 2022
• Journal: European Journal of Cancer
• Print ISSN: 0959-8049
• Electronic ISSN: 1879-0852
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 147
• Pages: 106-116
• DOI: https://doi.org/10.1016/j.ejca.2021.01.029
• Keywords: Carvedilol, Breast cancer, Metastasis, β-adrenergic, Survival.
• Public URL: https://nottingham-repository.worktribe.com/output/5369341
• Publisher URL: https://www.ejcancer.com/article/S0959-8049(21)00049-6/fulltext