To Örebro University

BACKGROUND: Chronic stress has been suggested to play a role in cancer progression, but few studies have so far examined the potential influence of stress susceptibility. This national register-based cohort study utilizes a unique data source to investigate whether a stress resilience measure is associated with survival in cancer patients.

METHODS: The cohort includes 9,318 Swedish male cancer patients born during 1952-1956 who had their stress resilience evaluated at a semi-structured interview with a psychologist during mandatory conscription examination in late adolescence.

RESULTS: Over a median of 3 years of follow-up from cancer diagnosis, a total of 2,541 patients died (2,322 from cancer). Overall, low (23%) compared with high (25%) stress resilience was associated with increased mortality (adjusted hazard ratio estimated by Cox regression 1.45; 95% confidence interval 1.28-1.65), particularly among men with carcinomas of the oropharynx (2.62, 1.24-5.56), upper respiratory tract (4.64, 1.05-20.41), and prostate (2.20, 1.04-4.62), as well as with Hodgkin's lymphoma (3.52, 1.40-8.86). An association was evident both for cancer types associated with smoking (1.35, 1.10-1.66) and malignancies without an established smoking aetiology (1.32, 1.12-1.56). The association between low stress resilience and mortality could partly be explained by tumour stage, marital status, and psychiatric comorbidity at cancer diagnosis.

CONCLUSIONS: We observed an association between low stress resilience and mortality among men diagnosed with cancer, particularly, oropharyngeal cancer, upper respiratory tract cancers, prostate cancer and Hodgkin's lymphoma.

IMPACT: These results suggest that individual variation in stress resilience may influence survival among men with some cancer types.

Preclinical studies have suggested that beta-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 (n = 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 (n = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70-0.90; P < 0.001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis (n = 517; adjusted HR, 0.60; 95% CI, 0.43-0.83; P = 0.002), especially for users with higher daily doses (HR, 0.54; 95% CI, 0.35-0.83; P = 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.

BACKGROUND: Beta-adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for non-small cell lung cancer (NSCLC) patients is contradictory and limited to small hospital-based studies. We therefore aimed to investigate if β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date.

PATIENTS AND METHODS: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between beta-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register.

RESULTS: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with non-use, beta-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [hazard ratio (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific beta-blockers and some histopathological subtypes exist cannot be excluded.

CONCLUSION: In this nationwide cohort of NSCLC patients, beta-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some beta-blockers is less conclusive.

IMPACT: Our results do not indicate that beta-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in NSCLC patients.