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Barron T.I.,St James's Hospital | Sharp L.,National Cancer Registry Ireland | Visvanathan K.,Johns Hopkins University
Therapeutic Advances in Medical Oncology | Year: 2012

The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between β-blockers and breast cancer progression. Preclinical studies have shown that β-adrenergic receptor (β-AR) signalling can inhibit multiple cellular processes involved in breast cancer progression and metastasis, including extracellular matrix invasion, expression of inflammatory and chemotactic cytokines, angiogenesis and tumour immune responses. This has led to the hypothesis that the commonly prescribed class of β-AR antagonist drugs (β-blockers) may favourably impact cancer progression. A number of recent pharmacoepidemiological studies have examined the association between β-blocker exposure and breast cancer progression. The results from these studies have suggested a potential role for targeting the β-AR pathway in breast cancer patients. Larger observational studies are, however, required to confirm these results. Questions regarding the type of β-blocker, predictive biomarkers or tumour characteristics, appropriate treatment paradigms and, most importantly, efficacy must also be answered in randomized clinical studies before β-blockers can be considered a therapeutic option for patients with breast cancer. © The Author(s), 2012.

Spillane S.,St James's Hospital | Bennett K.,St James's Hospital | Sharp L.,National Cancer Registry Ireland | Barron T.I.,St James's Hospital
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Background: Preclinical evidence suggests a beneficial effect of metformin in colorectal cancer. This study aimed to investigate associations between metformin exposure and colorectal cancer-specific survival using population-level data. Methods: Adult patients with stage I-III colorectal cancer diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland. Use of metformin and other antidiabetic medications was determined from a linked national prescription claims database. Multivariate Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between prediagnostic metformin exposure (versus nonmetformin antidiabetic drugs) and colorectal cancer-specific mortality. Models were stratified by antidiabetic drug coprescription and intensity of metformin exposure. Results: The cohort included 207 diabeticswho received metformin, 108 diabetics not exposed to metformin, and 3,501 nondiabetic patients. In multivariate analyses, a nonsignificant reduction in colorectal cancer-specific mortality was observed for metformin-exposed patients relative to other treated diabetics (HR, 0.61; 95% CI, 0.37-1.01). In stratified analyses, no significant association was observed for patients receiving low-intensity metformin or metformin in combination with other antidiabetic drugs. High-intensity exclusive metformin use was associated with a significant reduction in colorectal cancer-specific mortality (HR, 0.44; 95% CI, 0.20-0.95). Conclusions: Significant associations between metformin exposure and colorectal cancer-specific mortality were observed only for high-intensity exclusive metformin use in the diabetic cohort. Impact: This study provides moderate evidence of an association between metformin exposure and improved colorectal cancer survival in a diabetic population. Additional studies in larger cohorts, with detailed information on diabetes severity, are required to confirm these results. Cancer Epidemiol Biomarkers Prev; 22(8); 1364-73. ©2013 AACR.

Hanly P.,National College of Ireland | Soerjomataram I.,International Agency for Research on Cancer | Sharp L.,National Cancer Registry Ireland
International Journal of Cancer | Year: 2015

Every cancer-related death in someone of working age represents an economic loss to society. To inform priorities for cancer control, we estimated costs of lost productivity due to premature cancer-related mortality across Europe, for all cancers and by site, gender, region and country. Cancer deaths in 2008 were obtained from GLOBOCAN for 30 European countries across four regions. Costs were valued using the human capital approach. Years of productive life lost (YPLL) were computed by multiplying deaths between 15 and 64 years by working-life expectancy, then by country-, age- and gender-specific annual wages, corrected for workforce participation and unemployment. Lost productivity costs due to premature cancer-related mortality in Europe in 2008 were e75 billion. Male costs (e49 billion) were almost twice female costs (e26 billion). The most costly sites were lung (e17 billion; 23% of total costs), breast (e7 billion; 9%) and colorectum (e6 billion; 8%). Stomach cancer (in Southern and Central-Eastern Europe) and pancreatic cancer (in Northern and Western Europe) were also among the most costly sites. The average lost productivity cost per cancer death was e219,241. Melanoma had the highest cost per death (e312,798), followed by Hodgkin disease (e306,628) and brain and CNS cancer (e288,850). Premature mortality costs were 0.58% of 2008 European gross domestic product, highest in Central-Eastern Europe (0.81%) and lowest in Northern Europe (0.51%). Premature cancer-related mortality costs in Europe are significant. These results provide a novel perspective on the societal cancer burden and may be used to inform priority setting for cancer control. © 2014 UICC.

Hanly P.A.,National College of Ireland | Sharp L.,National Cancer Registry Ireland
BMC Cancer | Year: 2014

Background: Most measures of the cancer burden take a public health perspective. Cancer also has a significant economic impact on society. To assess this economic burden, we estimated years of potential productive life lost (YPPLL) and costs of lost productivity due to premature cancer-related mortality in Ireland.Methods: All cancers combined and the 10 sites accounting for most deaths in men and in women were considered. To compute YPPLL, deaths in 5-year age-bands between 15 and 64 years were multiplied by average working-life expectancy. Valuation of costs, using the human capital approach, involved multiplying YPPLL by age-and-gender specific gross wages, and adjusting for unemployment and workforce participation. Sensitivity analyses were conducted around retirement age and wage growth, labour force participation, employment and discount rates, and to explore the impact of including household production and caring costs. Costs were expressed in €2009.Results: Total YPPLL was lower in men than women (men = 10,873; women = 12,119). Premature cancer-related mortality costs were higher in men (men: total cost = €332 million, cost/death = €290,172, cost/YPPLL = €30,558; women: total cost = €177 million, cost/death = €159,959, cost/YPPLL = €14,628). Lung cancer had the highest premature mortality cost (€84.0 million; 16.5% of total costs), followed by cancers of the colorectum (€49.6 million; 9.7%), breast (€49.4 million; 9.7%) and brain & CNS (€42.4 million: 8.3%). The total economic cost of premature cancer-related mortality in Ireland amounted to €509.5 million or 0.3% of gross domestic product. An increase of one year in the retirement age increased the total all-cancer premature mortality cost by 9.9% for men and 5.9% for women. The inclusion of household production and caring costs increased the total cost to €945.7 million.Conclusion: Lost productivity costs due to cancer-related premature mortality are significant. The higher premature mortality cost in males than females reflects higher wages and rates of workforce participation. Productivity costs provide an alternative perspective on the cancer burden on society and may inform cancer control policy decisions. © 2014 Hanly and Sharp; licensee BioMed Central Ltd.

Sharp L.,National Cancer Registry Ireland | McDevitt J.,National Cancer Registry Ireland | Carsin A.-E.,Center for Research in Environmental Epidemiology | Brown C.,National Cancer Registry Ireland | Comber H.,National Cancer Registry Ireland
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

Background: Some studies suggest smoking may result in poorer clinical outcomes in head and neck cancer, but the evidence is heterogeneous and some of it is poor quality. In a large, population-based, study we investigated: (i) whether smoking at diagnosis is an independent prognostic factor for cancer-specific survival in head and neck cancer; and (ii) whether the association varies by site and treatment. Methods: Head and neck cancers (ICD10 C01-C14, and C30-32) diagnosed from 1994 to 2009 were abstracted from the National Cancer Registry Ireland, and classified by smoking status at diagnosis. Follow-up was for 5 years or until December 31, 2010. Multivariate Cox proportional hazards models were used to compare cancer specific death rates in current, ex-, and never smokers. Subgroup analyses by site and treatment were conducted. Results: In total, 5,652 head and neck cancers were included. At diagnosis, 24% were never smokers, 20% ex-smokers, and 56% current smokers. Compared with never smokers, current smokers had a significantly raised death rate from cancer [multivariate HR, 1.36; 95% confidence interval (CI), 1.21-1.53]. The association was similar after restriction to squamous cell tumors. A significantly increased cancer-related death rate was seen for current smokers with oral cavity, pharyngeal, and laryngeal cancers. The association was stronger in surgically treated patients [HR, 1.49; 95% CI, 1.25-1.79; P(interaction) = 0.01]. Neither radiotherapy nor chemotherapy modified the effect of smoking. Conclusions: Patients with head and neck cancer who smoke at diagnosis have a significantly increased cancer death rate. Impact: Greater efforts are needed to encourage and support smoking cessation in those at risk of, and diagnosed with, head and neck cancer. ©2014 AACR.

Flahavan E.M.,Trinity College Dublin | Bennett K.,Trinity College Dublin | Sharp L.,National Cancer Registry Ireland | Barron T.I.,Trinity College Dublin
Annals of Oncology | Year: 2014

Background: Aspirin use has been associated with reduced mortality from cancer including prostate cancer in some studies. A number of anti-cancer mechanisms of aspirin have been proposed, including the inhibition of the cyclooxygenase enzymes, through which aspirin mediates both anti-platelet and anti-inflammatory activities. This cohort study examines associations between pre-diagnostic aspirin use (overall and by dose and dosing intensity) and mortality in men with localised prostate cancer. Patients and methods: Men with stage I-III prostate cancer were identified from Irish National Cancer Registry records, which have been linked to national prescribing data from the Irish General Medical Services scheme. Aspirin use in the year preceding prostate cancer diagnosis was identified from this linked prescription-claims data. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for associations between aspirin use and all-cause and prostate cancer-specific mortality. Associations between prescribed dose and dosing intensity were examined. The presence of effect modification by the type of treatment received and tumour characteristics was also assessed. Results: Two thousand nine hundred and thirty-six men with a diagnosis of stage I-III prostate cancer (2001-2006) were identified (aspirin users, n = 1131). The median duration of patient follow-up was 5.5 years. In adjusted analyses, aspirin use was associated with a small, but non-significant, reduced risk of prostate cancer-specific mortality (HR = 0.88, 95% CI 0.67-1.15). In dose-response analyses, stronger associations with prostate cancer-specific mortality were observed in men with higher aspirin dosing intensity (HR = 0.73, 95% CI 0.51-1.05) and in men receiving >75 mg of aspirin (HR = 0.61, 95% CI 0.37-0.99). Analyses of effect modification by treatment type or tumour characteristics were non-significant. Conclusions: Consistent with prior studies, aspirin use was associated with a non-significant reduced risk of prostate cancer-specific mortality in men with localised prostate cancer. Men receiving higher doses of aspirin had a statistically significant reduced risk of prostate cancer-specific mortality. These findings regarding an aspirin dose require further investigation. © The Author 2013.Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Hanly P.,National Cancer Registry Ireland | Timmons A.,National Cancer Registry Ireland | Walsh P.M.,National Cancer Registry Ireland | Sharp L.,National Cancer Registry Ireland
Value in Health | Year: 2012

Objectives: Productivity costs constitute a substantial proportion of the total societal costs associated with cancer. We compared the results of applying two different analytical methods - the traditional human capital approach (HCA) and the emerging friction cost approach (FCA) - to estimate breast and prostate cancer productivity costs in Ireland in 2008. Methods: Data from a survey of breast and prostate cancer patients were combined with population-level survival estimates and a national wage data set to calculate costs of temporary disability (cancer-related work absence), permanent disability (workforce departure, reduced working hours), and premature mortality. Results: For breast cancer, productivity costs per person using the HCA were €193,425 and those per person using the FCA were €8,103; for prostate cancer, the comparable estimates were €109,154 and €8,205, respectively. The HCA generated higher costs for younger patients (breast cancer) because of greater lifetime earning potential. In contrast, the FCA resulted in higher productivity costs for older male patients (prostate cancer) commensurate with higher earning capacity over a shorter time period. Reduced working hours postcancer was a key driver of total HCA productivity costs. HCA costs were sensitive to assumptions about discount and growth rates. FCA costs were sensitive to assumptions about the friction period. Conclusions: The magnitude of the estimates obtained in this study illustrates the importance of including productivity costs when considering the economic impact of illness. Vastly different results emerge from the application of the HCA and the FCA, and this finding emphasizes the importance of choosing the study perspective carefully and being explicit about assumptions that underpin the methods. © 2012, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

De Camargo Cancela M.,National Cancer Registry Ireland | Comber H.,National Cancer Registry Ireland | Sharp L.,National Cancer Registry Ireland
British Journal of Cancer | Year: 2013

Background:Geriatric oncology guidelines state that fit older men with prostate cancer should receive curative treatment. In a population-based study, we investigated associations between age and non-receipt of curative treatment in men with localised prostate cancer, and the effect of clinical variables on this in different age groups.Methods:Clinically localised prostate cancers (T1-T2N0M0) diagnosed from 2002 to 2008 among men aged ≥40 years, with hospital in-patient episode(s) within 1 year post-diagnosis, were included (n=5456). Clinical and socio-demographic variables were obtained from cancer registrations. Comorbidity was determined from hospital episode data. Logistic regression was used to investigate associations between age and non-receipt of treatment, adjusting for confounders; the outcome was non-receipt of curative treatment (radical prostatectomy or radiotherapy).Results:The percentage who did not receive curative treatment was 9.2%, 14.3%, 48.2% and 91.7% for men aged 40-59, 60-69, 70-79 and 80+ years, respectively. After adjusting for clinical and socio-demographic factors, age remained the main determinant of treatment non-receipt. Men aged 70-79 had a significant five-fold increased risk of not having curative treatment compared with men aged 60-69 (odds ratio (OR)=5.5; 95% confidence interval 4.7, 6.5). In age-stratified analyses, clinical factors had a higher weight for men aged 60-69 than in other age strata. Over time, non-receipt of curative treatment increased among men aged 40-59 and decreased among men aged 70-79.Conclusion:Age remains the dominant factor in determining non-receipt of curative treatment. There have been some changes in clinical practice over time, but whether these will impact on prostate cancer mortality remains to be established. © 2013 Cancer Research UK. All rights reserved.

Barron T.I.,Trinity College Dublin | Cahir C.,Trinity College Dublin | Sharp L.,National Cancer Registry Ireland | Bennett K.,Trinity College Dublin
British Journal of Cancer | Year: 2013

Background:Non-persistence and non-compliance are common in women prescribed hormonal therapy for breast cancer, but little is known about their influence on recurrence.Methods:A nested case-control study of associations between hormonal therapy non-persistence and non-compliance and the risk of early recurrence in women with stage I-III breast cancer was undertaken. Cases, defined as women with a breast cancer recurrence within 4 years of hormonal therapy initiation, were matched to controls (1: 5) by tumour stage and age. Conditional logistic regression was used to examine associations between early recurrence and hormonal therapy non-persistence and non-compliance.Results:Ninety-four women with breast cancer recurrence were matched to 458 controls. Women who were non-persistent (≥180 days without hormonal therapy) had a significantly increased adjusted recurrence odds ratio (OR) of 2.88 (95%CI 1.11, 7.46) compared with persistent women. There was no significant association between low compliance (OR 1.30; 95% CI 0.74, 2.30) and breast cancer recurrence.Conclusion:Hormonal therapy non-persistence is associated with a significantly higher risk of early recurrence in women with stage I-III oestrogen receptor (ER)-positive breast cancer. This finding is consistent with results from randomized studies of hormonal therapy treatment duration and suggests that interventions to target modifiable risk factors for non-persistence are required. © 2013 Cancer Research UK.

Sharp L.,National Cancer Registry Ireland | Timmons A.,National Cancer Registry Ireland
Journal of Cancer Survivorship | Year: 2011

Introduction: Around 40% of cancer survivors are of working age. We investigated employment outcomes among survivors in Ireland where sick leave and sick pay are at the employers' discretion and the law affords no protection against dismissal following extended absence. Methods: A questionnaire was mailed to 1,373 survivors, identified from the National Cancer Registry, 6-24 months post-diagnosis. The analysis included breast and prostate cancer respondents who were working at diagnosis. Factors associated with work continuation post-diagnosis and work resumption after cancer-related absence were identified using logistic regression. Results: The response rate was 54%. Three hundred forty-six respondents were working at diagnosis (breast cancer = 246; prostate cancer = 100). Sixty-two (18%) continued working post-diagnosis. Factors significantly associated with work continuation were: self-employment, prostate cancer, lower pre-diagnosis household income, and not having surgery. Two hundred eighty-four took time off work post-diagnosis; of these, 51 (18%) had left the workforce, 187 (66%) had resumed working, and 46 (16%) planned to resume working. Factors significantly associated with work resumption were: tertiary education, not having chemotherapy, receiving sick pay, and not having a medical card (which provides free access to public health services). Among those who resumed working, the median absence was 30.1 weeks (inter-quartile range = 12.9-51.6). The length of absence varied significantly by socio-demographic, financial, medical, and job- and social welfare-related factors. Median working hours pre- and post-diagnosis differed significantly (pre-diagnosis = 38/week; post-diagnosis = 30/week; p<0.001). Conclusions: The high level of workforce departure and associations between self-employment, sick pay and medical cards, and employment outcomes suggest that social welfare and legal provisions are important determinants of the survivors' workforce participation. Implications for survivors: In formulating strategies to optimise survivors' employment outcomes, it is important that policy- and decision-makers are aware of the influence of social welfare and legal provisions. © 2011 Springer Science+Business Media, LLC.

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