Thomas I Barron

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States

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Publications (12)52.86 Total impact

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    ABSTRACT: Lymph node-positive breast tumors are more likely to express COX2 than node-negative tumors. In preclinical studies, COX2 inhibition prevents breast tumor spread to lymph nodes. Therefore, we examined the association between recent (1 year) prediagnostic use of aspirin (COX1/COX2 inhibitor), lymph node involvement at breast cancer diagnosis, and breast cancer-specific mortality. Women with stage I-III breast cancer diagnosed from 2001 to 2006 (N = 2,796) were identified from Ireland's National Cancer Registry. These data were linked to prescription refill and mammographic screening databases. Relative risks (RR) were estimated for associations between prediagnostic aspirin use and lymph node-positive status at diagnosis. HRs were estimated for associations between pre- and postdiagnostic aspirin use and 5-year mortality, stratified by lymph node status. Women with prediagnostic aspirin use were statistically significantly less likely to present with a lymph node-positive tumor than nonusers [RR = 0.89; 95% confidence interval (CI), 0.81-0.97], particularly those with larger (Pinteraction = 0.036), progesterone receptor (PR)-negative (Pinteraction < 0.001) or estrogen receptor (ER)-negative (Pinteraction = 0.056) tumors. The magnitude of this association increased with dose (Ptrend < 0.01) and dosing intensity (Ptrend < 0.001) and was similar in women with or without screen-detected tumors (Pinteraction = 0.70). Prediagnostic aspirin use was associated with lower 5-year breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.55; 95% CI, 0.33-0.92) but not node-positive tumors (HR, 0.91; 95% CI, 0.37-1.22). Tests for effect-modification were, however, not statistically significant (Pinteraction = 0.087). Postdiagnostic aspirin use was not associated with breast cancer-specific mortality (HR, 0.99; 95% CI, 0.68-1.45). Our findings indicate that recent prediagnostic aspirin use is protective against lymph node-positive breast cancer. This is a plausible explanation for reductions in breast cancer mortality reported in observational studies of aspirin use. Cancer Res; 74(15); 4065-77. ©2014 AACR.
    Cancer research. 08/2014; 74(15):4065-77.
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    ABSTRACT: Prostate cancer incidence has risen considerably in recent years, primarily due to Prostate Specific Antigen (PSA) testing in primary care. The objective of this study was to investigate associations between PSA testing and the psychological and physical health, and healthcare utilisation of men in a population where PSA testing is widespread.
    BMC Family Practice 06/2014; 15(1):121. · 1.61 Impact Factor
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    ABSTRACT: Preclinical evidence suggests a role for metformin in inhibiting tumour dissemination and metastasis. Previous studies have identified associations between metformin exposure and improved colorectal cancer survival. This study aimed to examine associations between metformin exposure and the odds of presenting with disseminated disease among colorectal cancer patients. Colorectal cancer patients diagnosed 2001-2006 were identified from the National Cancer Registry Ireland. A linked national pharmacy claims database was used to determine exposure to anti-diabetic medications prior to diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for associations between metformin use (versus non-metformin anti-diabetic drugs) and odds of presenting with disseminated disease (lymph node positive/metastatic). Analyses were stratified by anti-diabetic drug co-prescription and intensity of metformin exposure. The study population included 241 metformin-exposed diabetics, 129 non-metformin-exposed diabetics, and 4277 non-diabetic patients. In multivariate analysis, odds of disseminated disease were lower in metformin-exposed diabetics, compared with non-metformin-exposed diabetics, though not statistically significant (OR=0.66, 95% CI 0.39-1.12). In analyses stratified by metformin dosing intensity and anti-diabetic drug co-prescription, the odds were further from unity and approached significance in diabetics with high intensity, exclusive metformin use (OR=0.52, 95% CI 0.25-1.10). While overall there was no statistically significant association between metformin exposure and disseminated colorectal cancer at diagnosis, there was a suggestion that high intensity, exclusive metformin use may be associated with reduced odds of disseminated disease. The number of patients in these subgroup analyses was small, and further investigation in larger studies is warranted.
    Cancer epidemiology. 01/2014;
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    ABSTRACT: 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. 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. 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. 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.
    Annals of Oncology 01/2014; 25(1):154-9. · 7.38 Impact Factor
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    T I Barron, C Cahir, L Sharp, K Bennett
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    ABSTRACT: 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.British Journal of Cancer advance online publication, 3 September 2013; doi:10.1038/bjc.2013.518 www.bjcancer.com.
    British Journal of Cancer 09/2013; · 5.08 Impact Factor
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    ABSTRACT: To examine the association between digoxin exposure and mortality in men with prostate cancer using linked Irish National Cancer Registry and pharmacy claims data. Prostate cancer cases were identified from the database and digoxin exposure at prostate cancer diagnosis was identified from prescription claims. Digoxin users were matched to non-users using a propensity score to identify men with similar cardiovascular comorbidity. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between digoxin exposure and all-cause and prostate cancer-specific mortality (PCSM). Analyses were repeated in the propensity score-matched cohort. Effect modification of treatment with radiation or androgen-deprivation therapy by digoxin exposure was also assessed. In all, 5732 men with a prostate cancer diagnosis (2001-2006) were identified (digoxin exposed, 391). The median follow-up was 4.3 years. Digoxin exposure was associated with a small non-significant increase in PCSM in the full cohort (HR 1.13, 95% CI 0.91, 1.42) and the propensity. score-matched cohort (HR 1.17, 95% CI 0.88, 1.57). Adjusted HRs for all-cause mortality were increased for digoxin exposed men (HR 1.24, 95% CI 1.07, 1.43). Interactions with treatments received were not significant. These results suggest digoxin exposure is not associated with reduced PCSM. Further investigation of other cardiac glycosides that have shown anti-cancer potential may be warranted.
    BJU International 06/2013; · 3.05 Impact Factor
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    ABSTRACT: 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 stage I-III colorectal cancer patients diagnosed 2001-2006 were identified from the National Cancer Registry Ireland. Use of metformin and other anti-diabetic 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 pre-diagnostic metformin exposure (versus non-metformin anti-diabetic drugs) and colorectal cancer-specific mortality. Models were stratified by anti-diabetic drug co-prescription and intensity of metformin exposure. Results: The cohort included 207 diabetics who received metformin, 108 diabetics not exposed to metformin, and 3501 non-diabetic patients. In multivariate analyses a non-significant 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 anti-diabetic 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 Epidemiology Biomarkers &amp Prevention 06/2013; · 4.56 Impact Factor
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    Thomas I Barron, Linda Sharp, Kala Visvanathan
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    ABSTRACT: 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.
    rapeutic Advances in Medical Oncology, The 05/2012; 4(3):113-25.
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    ABSTRACT: Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality. Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed. Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers. The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.
    Journal of Clinical Oncology 05/2011; 29(19):2635-44. · 18.04 Impact Factor
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    ABSTRACT: Five years of treatment provides the optimum duration of tamoxifen therapy for the prevention of breast cancer recurrence and mortality. Durations of adjuvant tamoxifen therapy less than 5 years are associated with poorer outcomes for breast cancer patients. The purpose of the study was to assess rates of tamoxifen nonpersistence (early discontinuation) in women aged 35 years or older using prescription refill data from a national prescribing database. A cohort of 2816 women commencing tamoxifen as initial hormonal therapy was identified between January 2001 and January 2004. The cumulative tamoxifen persistence rate was calculated for these women and the relation between nonpersistence and clinical and demographic variables assessed. Within 1 year of commencing treatment the cumulative tamoxifen nonpersistence rate was 22.1%. This is twice the rate of treatment discontinuation observed in other studies by this time. By the end of follow-up at 3.5 years, the cumulative nonpersistence rate had increased to 35.2%. Determinants of nonpersistence identified included age and a history of antidepressant use. The rate of nonpersistence with tamoxifen therapy is higher than previously reported. This study demonstrates that persistence with tamoxifen cannot be assumed and raises concerns about persistence with other oral hormonal therapies for breast cancer and oral antineoplastics in general. Oncologists need to identify those at risk of nonpersistence and develop strategies to combat this barrier to treatment success.
    Cancer 04/2007; 109(5):832-9. · 5.20 Impact Factor
  • Thomas I Barron, Kathleen Bennett, John Feely
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    ABSTRACT: The PROVE-IT and REVERSAL studies established that an intensive 80 mg/day dose of atorvastatin was superior to pravastatin 40 mg/day for the secondary prevention of coronary heart disease (CHD) following acute coronary syndromes and in limiting the progression of coronary atherosclerosis. We have evaluated the impact of the results from these studies on statin prescribing by hospital doctors in the 2 years following their publication. Using a nationwide database, 18,894 patients receiving a total of 23,750 hospital discharge prescriptions for atorvastatin were identified between September 2002 and December 2005. From this cohort, patients newly commenced on, switched to, or dose titrated on atorvastatin by a hospital prescriber were identified. The mean daily atorvastatin dose on discharge was calculated for each month and the results were analysed using a segmented regression analysis. There was a significant and sustained increase in the mean atorvastatin dose used by hospital prescribers. This resulted in an increase of 12 mg, (95% CI 10.6, 13.4) in the mean dose prescribed by December 2005. This was attributable largely to a 16.4% (95% CI 13.5, 19.3), 17.2% (95% CI 14.0, 20.5) and 8.8% (95% CI 7.4, 10.2) increase in the prescribing of the 20 mg, 40 mg and 80 mg/day dosages, respectively. The PROVE-IT and REVERSAL studies have had a significant impact on hospital prescribers' choice of atorvastatin dose. It is likely that this has been the result of both the publication and effective promotion of results from these trials.
    European Journal of Clinical Pharmacology 02/2007; 63(1):65-72. · 2.74 Impact Factor
  • Thomas I. Barron, Roisin M. Connolly, John Feely
    Cancer 01/2007; 110(11):2596-2596. · 5.20 Impact Factor

Publication Stats

221 Citations
52.86 Total Impact Points

Institutions

  • 2014
    • Johns Hopkins Bloomberg School of Public Health
      Baltimore, Maryland, United States
  • 2012–2014
    • St. James's Hospital
      Dublin, Leinster, Ireland
  • 2011–2013
    • Dublin City University
      Dublin, Leinster, Ireland
  • 2007–2013
    • Trinity College Dublin
      • Department of Pharmacology and Therapeutics
      Dublin, L, Ireland