Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma

Abstract

Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register ( = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score, and other medications to estimate HRs and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90-day period before cancer diagnosis. A total of 2,054 (86%) died, with pancreatic cancer recorded as the underlying cause of death during a maximum of 5-year follow-up (median 5 months). Patients who used beta-blockers ( = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70-0.90; < 0.001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis ( = 517; adjusted HR, 0.60; 95% CI, 0.43-0.83; = 0.002), especially for users with higher daily doses (HR, 0.54; 95% CI, 0.35-0.83; = 0.005). No clear rate differences were observed by beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease. .

β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

“…β1-selective drugs provide no clinical advantage, consistent with our in vitro studies showing that atenolol did not suppress proliferation of Kras mutant pancreatic cells. Among the 2394 patients in a very recent study (Udumyan et al, 2017), only 21 were NSBB patients. Nevertheless, patients who used β-blockers (n=522) had a lower cancer-specific mortality rate than nonusers.…”

“…In addition, cancer mortality is significantly increased by high levels of psychological stress (Batty et al, 2017). On the other hand, it is suggested that β-blocker treatment of patients suffering from colorectal cancer (Jansen et al, 2014), breast cancer (Barron et al, 2011), ovarian cancer (Watkins et al, 2015), melanoma (Lemeshow et al, 2011), and PDAC (Beg et al, 2017; Udumyan et al, 2017), may lead to improved survival.…”

Effect of beta-blockers on cancer recurrence and survival: a meta-analysis of epidemiological and perioperative studies

“…Seven studies (six retrospective 24,31,37,39,41,42 and one prospective 44 ) examined the effect of 'non-selective' beta-blocker use on OS. The pooled HR for all cancer types was not statistically significant.…”

Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

“…However encouraging the results from experimental studies may be, the role of beta-blockers in cancer patients remains unclear and the results from mostly retrospective observational studies are equivocal. There are studies suggesting the use of beta-blockers may be able to prolong survival of cancer patients [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. On the other hand, there are also studies that do not support such a hypothesis [50][51][52][53][54][55][56][57][58][59][60].…”