Recent studies have indicated that β-adrenergic signaling is involved in the regulation of immune responses to breast tumor cells, and data from in vivo studies show an association between β-adrenergic signaling with increased nodal involvement and development of metastasis but no effect on primary tumor growth. Based on this evidence, Dr Thomas I. Barron, from the department of pharmacology and therapeutics at Trinity Centre for Health Sciences, in Dublin, Ireland, and colleagues chose to explore the relationship between beta blocker use and breast tumor characteristics as well as breast cancer morbidity.
Recent studies have indicated that β-adrenergic signaling is involved in the regulation of immune responses to breast tumor cells, and data from in vivo studies show an association between β-adrenergic signaling with increased nodal involvement and development of metastasis but no effect on primary tumor growth. Based on this evidence, Dr Thomas I. Barron, from the department of pharmacology and therapeutics at Trinity Centre for Health Sciences, in Dublin, Ireland, and colleagues chose to explore the relationship between beta blocker use and breast tumor characteristics as well as breast cancer morbidity.
The researchers hypothesized that β2 receptor activity prior to diagnosis of breast cancer would result in a lower risk of local tumor invasion, nodal involvement, or metastatic disease. They further believed that continued use of beta blockers would result in a decrease in mortality. Using a national cancer registry in Ireland and Ireland’s General Medical Service prescription dispensing data, Barron and colleagues conducted a case-control study with women aged 40 years or older with a diagnosis of stage I to stage IV invasive breast cancer. Women who were taking either propranolol (n = 70) or atenolol (n = 525) were matched with controls (n = 4738) from the same base population. Patients were followed up between 1 and 5 years after breast cancer diagnosis. In the year before diagnosis, there was a median exposure of 232 days and a median daily dose of 80 mg for propranolol.
Participants taking propranolol were significantly less likely to present with a T4 tumor at diagnosis or N2/N3 nodal involvement or metastatic disease compared with nonusers matched by age, comorbidity, and propensity score. In addition, the researchers found an 81% lower risk for breast cancer–specific mortality at 5 years after breast cancer diagnosis when compared to those women who did not take propranolol. Moreover, women who used propranolol longer had fewer T4 tumors. The researchers believe this hints at a dose-response relationship.
Atenolol use, however, did not appear to confer the same protective properties. No difference was found in breast cancer–specific mortality between women who were taking atenolol as compared to the matched women who were not taking atenolol. Indeed, they did not find an association between any of the study outcomes with the use of atenolol, which is a β1-selective antagonist (as compared to propranolol, which is a β2-selective antagonist).
“The results presented here provide evidence in humans that confirm in vivo and in vitro observations that antagonism of the β-adrenergic receptor alters its signaling and subsequent tumor-related sequelae in a favorable manner,” Barron and colleagues concluded. “These results support the role of β-adrenergic signaling pathways in the regulation of breast tumor progression and suggest that interventions targeting these pathways may complement existing breast cancer therapies.”
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Reference
Barron TI, Connolly RM, Sharp L, et al.Beta blockers and breast cancer mortality: a population-based study. J Clin Oncol. 2011;29(19):2635-44.
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