Hazard ratios for breast cancer mortality by deprivation stratum, Ireland, 1999–2008: by (a) age of diagnosis and (age-adjusted) by (b) region of residence, (c) Charlson Index of comorbidity, (d) TNM 5^th-edition stage, (e) method of presentation, and (f) surgical and hormonal treatment.

<p>Trends by deprivation were less heterogeneous for other subgroups.</p

Five-year cause-specific survival (age-standardized) and age-adjusted mortality hazard ratios for female breast cancer patients, Ireland, 1994–2008: by deprivation stratum and diagnosis cohort.

<p>Five-year cause-specific survival (age-standardized) and age-adjusted mortality hazard ratios for female breast cancer patients, Ireland, 1994–2008: by deprivation stratum and diagnosis cohort.</p

Five-year (a) and ten-year (b) cause-specific survival of female breast cancer patients, Ireland, 1999–2008: by deprivation stratum, all ages (age-standardized) and by diagnosis age.

<p>Five-year (a) and ten-year (b) cause-specific survival of female breast cancer patients, Ireland, 1999–2008: by deprivation stratum, all ages (age-standardized) and by diagnosis age.</p

Hazard ratios for cause-specific mortality by deprivation stratum for female breast cancer patients, Ireland, 1999–2008.

<p>(See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111729#pone-0111729-t002" target="_blank">Table 2</a> for fuller details of Model C.).</p>a<p><i>Model A:</i> stratified by age (to allow for non-proportional hazards).</p>b<p><i>Model B:</i> as model A but also stratified for T, N and M categories of stage.</p>c<p><i>Model C:</i> as model B but also stratified for tumour grade, and adjusted for method of presentation, smoking status, region of residence, diagnosis year, tumour morphology and hormone receptor status; standard errors adjusted for clustering by region of residence; marital status and HER2 status excluded as they did not significantly contribute to model-fit); Charlson Index of co-morbidity (available for 82% of cases 2002–2008) excluded as it did not contribute significantly to model-fit.</p>d<p><i>Model D:</i> as model C but also adjusted for treatments within 12 months after diagnosis: breast surgery (mastectomy, BCS, or none); radiotherapy (month of treatment, or none); chemotherapy & other non-hormonal medical oncology (month of treatment, or none); hormone therapy (< = median month to treatment, yes>median, none); any tumour-directed treatment (yes, no); regional lymph-node excision/biopsy (yes/no). Time to surgical treatment or to first tumour-directed treatment did not improve model fit further.</p><p>* P<0.05, ** P<0.01, *** P<0.001.</p><p>Hazard ratios for cause-specific mortality by deprivation stratum for female breast cancer patients, Ireland, 1999–2008.</p

Case numbers, incidence and summary of patient and tumour characteristics variables (those showing significant variation) by area-based deprivation stratum for female breast cancer in Ireland, 1999–2008.^a

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111729#pone-0111729-g002" target="_blank">Figure 2</a> for treatment variation by deprivation stratum.</p><p>*P<0.05, **P<0.01, ***P<0.001.</p><p>#Age-adjusted relative risks for stratum 5 v 1, and for average per-unit change across deprivation strata 1–5, exclude unknown values for relevant patient, tumour and treatment variables. ^aFuller details of tumour and patient characteristics (e.g. finer age-groups) were used in statistical modeling of survival. ^bEuropean age-standa<i>r</i>dized rate (per 100,0000 women per year). ^cAge-standardized incidence ratio. ^dCases used for survival analysis exclude: diagnosis age <15 or >99; cancers preceded by another breast cancer or other malignant cancer (excluding non-melanoma skin cancers); death-certificate-only, autopsy-only and other cases with diagnosis = death date. ^eCases with known comorbidity status (based on hospital patient linkage) 2002–2008: 13039 (82.4%) of 2002–2008 total 15827. ^fDeprivation stratum was unknown for 1826 cases (not shown separately).</p><p>Case numbers, incidence and summary of patient and tumour characteristics variables (those showing significant variation) by area-based deprivation stratum for female breast cancer in Ireland, 1999–2008.^a</p

Relative risks for breast cancer treatment by deprivation stratum, Ireland, 1999–2008: age-adjusted (black symbols) and fully adjusted (grey).

<p>Adjusted for diagnosis cohort, age-group, HSE area of residence, T, N and M categories of stage, tumour grade, method of presentation, smoking status, marital status (except hormone therapy), tumour morphology, hormone receptor status and HER2 status (except radiotherapy), also surgery type (for radiotherapy only).</p

Further details of model C (Table 2): other patient and tumour factors influencing breast cancer survival (in a model assessing the influence of area-based deprivation status), 1999–2008.

<p>Only factors which contributed significantly to model-fit are shown^a; hazard ratios for age, TNM and grade are not shown, as the model shown in parentheses for age, TNM and grade are from simpler, adjusted but unstratified models (the more definitive model was stratified for those variables).</p>a<p>Marital status and HER2 status excluded as they did not significantly contribute to model-fit); Charlson Index of co-morbidity (available for 82% of cases 2002–2008) excluded as it did not contribute significantly to model-fit (in 2002–2008 sub-analysis); standard errors adjusted for clustering by region of residence. Models adjusted for (or stratified by) coarser groupings of variables tabulated had a poorer fit to the data.</p><p>* P<0.05, ** P<0.01, *** P<0.001.</p><p>Further details of model C (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111729#pone-0111729-t002" target="_blank">Table 2</a>): other patient and tumour factors influencing breast cancer survival (in a model assessing the influence of area-based deprivation status), 1999–2008.</p

Hazard ratios for cause-specific mortality by deprivation stratum for female breast cancer patients, Ireland, 1999–2008: comparison of models from A (age-stratified) to D (fully adjusted).

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111729#pone-0111729-t002" target="_blank">Table 2</a> for further details of the models.</p

Estimated numbers of the separate types of CEs based on the assumption of 750 cardiac cases.

<p>Estimated numbers of the separate types of CEs based on the assumption of 750 cardiac cases.</p

Late Cardiac Events after Childhood Cancer: Methodological Aspects of the Pan-European Study PanCareSurFup

<div><p>Background and Aim</p><p>Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup.</p><p>Methods</p><p>Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors. Data on symptomatic heart failure, ischemia, pericarditis, valvular disease and arrhythmia were collected and graded according to the Criteria for Adverse Events. Detailed treatment data, data on potential confounders, lifestyle related risk factors and general health problems were collected.</p><p>Results</p><p>The PanCareSurFup cardiac cohort consisted of 59,915 5-year childhood cancer survivors with malignancies diagnosed between 1940 and 2009 and classified according to the International Classification of Childhood Cancer 3. Different strategies were used to identify cardiac events such as record linkage to population/ hospital or regional based databases, and patient- and general practitioner-based questionnaires.</p><p>Conclusion</p><p>The cardiac study of the European collaborative research project PanCareSurFup will provide the largest cohort of 5-year childhood cancer survivors with systematically ascertained and validated data on symptomatic cardiac events. The result of this study can provide information to minimize the burden of cardiac events in childhood cancer survivors by tailoring the follow-up of childhood cancer survivors at high risk of cardiac adverse events, transferring this knowledge into evidence-based clinical practice guidelines and providing a platform for future research studies in childhood cancer patients. </p></div