Abstract P3-11-05: Association between Propanolol Use and Both Breast Cancer Incidence and Mortality

Abstract

Abstract Background: The neurotransmitter epinephrine has been shown to promote breast cancer tumor cell migration, mediated through the ≥2 adrenergic pathway. In-vitro and in-vivo studies have demonstrated that the non-selective ≥1/≥2 adrenergic receptor antagonist propranolol inhibits the effects of epinephrine on breast cancer cell motility. Based on these studies we hypothesize that propranolol use prior to breast cancer diagnosis may result in a lower risk of locally advanced or metastatic disease at diagnosis and decrease the risk of breast cancer recurrence and mortality. Methods: To test these hypotheses we conducted a series of matched observational studies in a largely unscreened population, using pharmacy claims data linked to cancer registry data from the National Cancer Registry Ireland (NCRI, 2000-2007, n=5,949). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for stage at diagnosis. A Cox proportional hazard model was used to estimate the hazard ratio (HR) for breast cancer mortality. All analyses were repeated with atenolol, a selective ≥1 adrenergic receptor antagonist. Results: 71 patients taking propranolol in the year prior to breast cancer diagnosis were identified from the NCRI database (mean age 65; Stage-1 19.7%; Stage-2 57.8%; Stage-3 8.5%; Stage-4 8.5%; Unknown 5.6%). Patients taking propranolol in the year prior to breast cancer diagnosis were matched (1:2) using propensity scores to patients not taking a β-blocker by age, tumor grade, comorbidities, co-medications, demographics and socio-economic status. The odds of developing a T4 tumour for patients taking propranolol was OR 0.22, 95%CI 0.02, 0.98. (Atenolol: OR 1.29, 95%CI 0.83, 2.00). There was a twofold increase in the odds of developing a N0/M0 tumour (OR 2.02, 95%CI 1.03, 3.99) for patients taking propranolol in the year prior to breast cancer diagnosis compared to patients not taking a β-blocker after matching (1:2) for age, tumor size, tumor grade, and co-medications. (Atenolol OR 0.94, 95%CI 0.73, 1.19). Patients taking propranolol at the time of breast cancer diagnosis were matched to patients not taking a β-blocker (1:2) by age, tumor stage, tumor grade and comorbidities. At five years the cumulative probability of breast cancer death was 12.3% in patients taking propranolol and 33.3% in matched controls, HR 0.22, 95%CI 0.08, 0.61. (Atenolol HR 1.02, 95%CI 0.79, 1.31). Discussion: The use of propranolol, a non-selective ≥1/≥2 adrenergic receptor antagonist, results in a statistically significant reduction in the risk of locally advanced or metastatic breast cancer. The use of propranolol was also associated with a significant reduction in breast cancer mortality. No effect was observed with the use of a selective ≥1 adrenergic receptor antagonist. This suggests that the effects of propranolol in breast cancer are mediated through the ≥2 adrenergic pathway, supporting preclinical observations. To our knowledge, this is the first epidemiological study to examine the effects of propranolol on breast cancer stage at presentation and survival. Our results provide rationale for further investigation of this agent in breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-05.