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Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus 0– Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

Background The number of elderly cancer survivors is growing because of increasing survival rates. A high comorbidity burden in the elderly can affect their quality of life and survival. The aim of this study was to examine whether breast cancer survivors and population-based controls have a different comorbidity burden after long-term follow-up. Methods This study used data from a German breast cancer case-control study, which initially comprised 3813 breast cancer cases aged 50 to 74 years who were diagnosed between 2002 and 2005 and 7341 population-based controls. Participants were followed up in 2014/2016. A modified Charlson Comorbidity Index (mCCI) was calculated to quantify severe comorbidities. Negative binomial regression was performed to estimate rate ratios (RRs) with 95% confidence intervals (CIs) for the association between case-control status and mCCI (dependent variable) for the baseline population and for those who participated at follow-up, with adjustments made for relevant lifestyle factors. Results In total, 1925 cases and 3674 controls participated in the follow-up 12 years after recruitment. In the baseline population 35% had at least 1 comorbid condition.In long-term survivors this proportion was 52%. No difference was found in the mCCI between breast cancer cases and controls at baseline (RR, 1.05; 95% CI, 0.98-1.11) or between long-term survivors of the 2 groups at baseline (RR, 1.07; 95% CI, 0.97-1.18) or at follow-up (RR, 1.00; 95% CI, 0.91-1.10). Conclusions The comorbidity burden of long-term breast cancer survivors and controls increased over time; however, it remained similar in both groups after 12 years of follow-up.

More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long-term breast cancer survivors. We used data from a prospective population-based patient cohort study (MARIE) conducted in two geographical regions of Germany. Breast cancer patients diagnosed 50 to 74 years of age with an incident invasive breast cancer or in situ tumor were recruited from 2002 to 2005 and followed up until June 2015. Baseline weight was ascertained at an in-person interview at recruitment and follow-up weight was ascertained by telephone interview in 2009. Delayed entry Cox proportional hazards regression was used to assess associations between relative weight change and all-cause mortality, breast cancer mortality, and recurrence-free survival. In total, 2216 patients were included. Compared to weight maintenance (within 5%), weight loss >10% increased risk of all-cause mortality (HR 2.50, 95% CI 1.61, 3.88), breast cancer mortality (HR 3.07, 95% CI 1.69, 5.60) and less so of recurrence-free survival (HR 1.43, 95% CI 0.87, 2.36). Large weight gain of >10% also increased all-cause mortality (HR 1.64, 95% CI 1.02, 2.62) and breast cancer mortality (HR 2.25, 95% CI 1.25, 4.04). Weight maintenance for up to 5 years in long-term breast cancer survivors may help improve survival and prognosis. Postdiagnosis fluctuations in body weight of greater than 10% may lead to increased mortality. Survivors should be recommended to avoid large deviations in body weight from diagnosis onwards to maintain health and prolong life.

Die korperliche Aktivitat stellt ein komplexes Verhalten dar, dessen valide und reliable Erfassung in gros angelegten populationsbasierten Studien mit besonderen Herausforderungen einhergeht. In der bundesweiten NAKO Gesundheitsstudie liegen zur Halbzeit der Basiserhebung die Daten zur korperlichen Aktivitat fur 100.000 Teilnehmende vor. Beschreibung der Erfassung der korperlichen Aktivitat und Prasentation erster deskriptiver Ergebnisse. Das multimodale Erhebungskonzept bestand aus zwei Fragebogen, dem Questionnaire on Annual Physical Activity Pattern (QUAP) und dem Global Physical Activity Questionnaire (GPAQ), einem computerbasierten Erinnerungsprotokoll der vergangenen 24 h (cpar24) und einer 7‑Tage-Akzelerometrie (Actigraph GT3X/+; Fa. ActiGraph, Pensacola, FL, USA). Fur die einzelnen Erhebungsmodule lagen auswertbare Datensatze in unterschiedlicher Zahl vor (QUAP: n = 16.372; GPAQ: n = 90.900; cpar24: n = 23.989; Akzelerometrie: n = 35.218). Die Analysen der einzelnen Module ergaben unterschiedliche Durchschnittswerte fur die moderate oder intensive korperliche Gesamtaktivitat der Teilnehmenden: Bei Frauen wurden 75–216 min/Tag gemessen, bei Mannern 73–224 min/Tag. Personen der Altersgruppe 20–39 Jahre verbrachten 66–200 min/Tag in moderater oder intensiver korperlicher Gesamtaktivitat, wahrend Personen der Altersgruppe 40–69 Jahre 78–244 min/Tag aufwendeten. Erste modulubergreifende Analysen der korperlichen Aktivitat in der NAKO zeigen den Nutzen komplementar eingesetzter Erhebungsmethoden. Die umfangreichen Daten stellen eine wertvolle Ressource fur die Charakterisierung der Zusammenhange zwischen korperlicher Aktivitat und Krankheitspravention dar, die in der Zukunft erfolgen soll.

Adipokines including leptin, adiponectin and resistin have been linked to risk of obesity-related cancers potentially through low-grade chronic inflammation pathways. We aimed to assess the role of post-diagnosis circulating adipokines on long-term prognosis in a prospective breast cancer cohort. Adipokines were measured in blood collected at baseline shortly after diagnosis (2002–2005) and at follow-up (2009) from 3112 breast cancer patients enrolled in the population-based MARIE study. Half of the patients had measurements at both time-points. All-cause mortality, breast cancer specific mortality and recurrences were ascertained up to June 2015 (11 years median follow-up). Associations with time-varying adipokine concentrations overall and stratified by estrogen and progesterone receptor (ERPR) were evaluated using adjusted proportional hazard regression. At baseline (n = 2700) and follow-up (n = 2027), median concentrations for leptin, adiponectin and resistin were 4.6 and 2.7 ng/ml, 24.4 and 30.0 mg/l, 15.4 and 26.2 ng/ml, respectively. After adjustment, there was no evidence for associations between adipokines and any outcome overall. In ERPR negative tumors, highest vs. lowest quintile of adiponectin was significantly associated with increased breast cancer specific mortality (HR 2.51, 95%CI 1.07–5.92). Overall, post-diagnosis adipokines were not associated with long-term outcomes after breast cancer. In patients with ERPR negative tumors, higher concentrations of adiponectin may be associated with increased breast cancer specific mortality and warrant further investigation.

It is unclear whether a breast cancer diagnosis affects health behaviour changes that occur with ageing. We aimed to compare long-term changes of alcohol consumption, body weight, and physical activity in women with breast cancer and in age-matched unaffected women.We used data from 1,925 women with breast cancer and 3,473 unaffected women aged 50-74 years enrolled in the population-based case-control study MARIE (Mamma Carcinoma Risk Factor Investigation) in 2002-2005, who also completed the follow-up in 2014-2016. Multinomial logistic regression was applied to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between breast cancer status and categories of change in alcohol consumption, weight and physical activity.After 11.6 years of follow-up, breast cancer survivors had significantly lower odds than unaffected women of increasing alcohol consumption from ≤10 to10 g/day (adjusted OR 0.48, 95 % CI 0.35-0.65), but were more likely to experience a major weight change of ≥10 % compared to having stable weight (±5 %) (OR for increase and decrease 1.32, 95 % CI 1.03-1.70 and 1.36, 95 % CI 1.05-1.77, resp.) and to decrease transport physical activity to below 2.5 h/week compared to maintaining the activity level (OR 1.61, 95 % CI 1.26-2.04). No significant group difference was found for changes in recreational physical activity.Our data indicate that some long-term health behaviour changes can be attributed to a breast cancer diagnosis rather than ageing, suggesting that long-term medical care of breast cancer survivors could pay greater attention to weight control and sufficient physical activity.

In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks.The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example.The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements.On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health.The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

Background Physical activity (PA) before and after breast cancer diagnosis has been reported to be associated with lower mortality. However, whether changes in the activity after diagnosis impact prognosis is unclear and has not received much attention. This study aimed to examine pre- to postdiagnosis leisure-time PA and breast cancer prognosis. Methods We used data from the MARIE study, a prospective population-based patient cohort study of 3813 postmenopausal breast cancer patients, aged 50–74 at diagnosis, recruited from 2002 to 2005, re-interviewed in 2009, and followed up until June 2015. Prediagnosis PA was assessed at recruitment; postdiagnosis PA was assessed at re-interview in 2009. To examine pre- to postdiagnosis change in PA, women were categorized by pre- and postdiagnosis PA using a cut-off of 7.5 MET-h/week for meeting PA recommendations and combined into four groups: insufficiently active, increasingly active, decreasingly active, and sufficiently active. Cox regression models with delayed entry were used to assess associations between pre- to postdiagnosis patterns of PA and overall mortality (OM), breast cancer mortality (BCM), and recurrence-free survival (RFS). Additional analyses of pre- and postdiagnosis PA (no activity (reference), low activity, sufficient activity) with cancer outcomes, such as using a time-dependent model, were performed. In total, 2042 patients were included in the analyses. Results There were 206 deaths (114 from breast cancer) after a median follow-up time of 6.0 years after the 2009 interview. Compared to insufficiently active women, increasingly active women were at lower risk of OM, BCM, and RFS (HR (95%CI) of 0.50 (0.31–0.82), 0.54 (0.30–1.00), 0.58 (0.40–0.84), respectively). In sufficiently active women, associations for OM (0.75 (0.48–1.15)), BCM (0.61 (0.33–1.13)), and RFS 0.80 (0.57–1.14)) were similar to increasingly active women but attenuated, and decreasingly active women were not at lower risk for OM (0.91 (0.61–1.36)), BCM (0.80 (0.45–1.42)), and RFS (1.04 (0.76–1.43)). In time-dependent analyses, sufficient activity vs. no activity was associated with better OM (0.73 (0.57–0.93)), BCM (0.64 (0.46–0.89)), and RFS (0.82 (0.68–0.99)). Low activity was not significantly associated with prognosis. Conclusion Our data support benefits for breast cancer prognosis in being physically active pre- and postdiagnosis particularly for women who were insufficiently active prediagnosis.

Lignans are associated with improved postmenopausal breast cancer (BC) survival, but whether these associations, particularly with enterolactone (major lignan metabolite), persist over time is unclear. Little is known about other phytoestrogens on prognosis in long-term survivors. The study examines associations of prognosis with 1) circulating postdiagnosis enterolactone, 2) eight circulating phytoestrogen metabolites, and 3) changes in enterolactone and genistein. In a German cohort of 2,105 postmenopausal BC patients with blood samples collected at recruitment 2002-2005 (baseline) and re-interview in 2009 (follow-up), delay-entry Cox proportional hazards regression was used. Landmark analysis showed that circulating enterolactone (log2) associations with 5-year survival changed over time, with strongest hazard ratios of 0.89 (95% CI, 0.80-0.99) at blood draw (BD) and 0.86 (0.77-0.97) at 2 years post-BD for BC mortality, and 0.87 (0.80-0.95) at BD and 0.84 (0.76-0.92) at 3 years post-BD for all-cause mortality, which attenuated thereafter. In long-term survivors, increasing concentrations of genistein (1.17, 1.01-1.36), resveratrol (1.19, 1.02-1.40), and luteolin (1.96, 1.07-3.58) measured in follow-up blood samples were associated with poorer subsequent prognosis. Neither enterolactone at follow-up nor changes in enterolactone/genistein were associated with prognosis. Large long-term longitudinal studies with multiple phytoestrogen measurements are required to understand long-term effects of phytoestrogens after BC.

Background: Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort.Methods: Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW).Results: Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHRIPTW 0.88, 0.35-2.12), other cancer mortality (SHRIPTW 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHRIPTW 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHRIPTW 0.39, 95% CI 0.17-0.90 and SHRIPTW 0.58, 95% CI 0.34-0.97, respectively).Conclusion: In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted. (C) 2017 Elsevier Ltd. All rights reserved.

Background Until now, herpes zoster (HZ)-related disease burden in Germany has been estimated based on health insurance data and clinical findings. However, the validity of self-reported HZ is unclear. This study investigated the validity of self-reported herpes zoster (HZ) and its complication postherpetic neuralgia (PHN) using data from the pretest studies of the German National Cohort (GNC) in comparison with estimates based on health insurance data. Methods Data of 4751 participants aged between 20 and 69 years from two pretest studies of the GNC carried out in 2011 and 2012 were used. Based on self-reports of physician-diagnosed HZ and PHN, age- and sex-specific HZ incidence rates and PHN proportions were estimated. For comparison, estimates based on statutory health insurance data from the German population were considered. Results Eleven percent (95%-CI, 10.4 to 12.3, n = 539) of the participants reported at least one HZ episode in their lifetime. Our estimated age-specific HZ incidence rates were lower than previous estimates based on statutory health insurance data. The PHN proportion in participants older than 50 years was 5.9% (1.9 to 13.9%), which was in line with estimates based on health insurance data. Conclusion As age- and sex-specific patterns were comparable with that in health insurance data, self-reported diagnosis of HZ seems to be a valid instrument for overall disease trends. Possible reasons for observed differences in incidence rates are recall bias in self-reported data or overestimation in health insurance data. Electronic supplementary material The online version of this article (10.1186/s12879-019-3691-2) contains supplementary material, which is available to authorized users.

We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed between 2001 and 2005 who were recruited in Germany for a population-based study, the Mamma Carcinoma Risk Factor Investigation (MARIE Study), and prospectively followed up until the end of 2009. Locoregional recurrence and distant metastasis were included as intermediate states, and deaths from breast cancer, secondary cancer, and other causes were included as competing absorbing states. Tumor characteristics were significantly associated with all breast cancer-related endpoints. Nodal involvement was significantly related to local recurrence but more strongly related to distant metastases. Smoking was significantly associated with mortality from second cancers and other causes, whereas menopausal hormone use was significantly associated with reduced distant metastasis and death from causes other than cancer. The presence of cardiovascular disease at diagnosis was solely associated with mortality from other causes. Compared with separate Cox models, multistate models allow for dissection of prognostic factors and intermediate events in the analysis of cause-specific mortality and can yield new insights into disease progression and associated pathways.

Background There is a paucity of information on the prevalence of dietary supplement use in breast cancer survivors. Only a few studies have examined the impact of dietary supplements, particularly antioxidants, on breast cancer prognosis and the results are inconclusive. Objective We examined pre- and postdiagnosis use of supplements in postmenopausal breast cancer survivors in Germany and investigated associations between postdiagnosis use of antioxidants and other supplements, and prognosis (total and breast cancer mortality, and recurrence-free survival) both overall and in women who received chemotherapy and radiation therapy. Design Data from 2223 postmenopausal women diagnosed with nonmetastatic breast cancer from the population-based Mamma Carcinoma Risk Factor Investigation (MARIE) study were used. Women were interviewed at recruitment in 2002-2005 and again in 2009 and followed-up until 30 June 2015. Multivariate Cox regression analysis was used to estimate HRs and corresponding 95% CIs. Results Pre- and postdiagnosis supplement use was reported by 36% and 45% of the women, respectively. There were 240 deaths (134 from breast cancer) and 200 breast cancer recurrences after a median follow-up time of 6.0 y after the 2009 re-interview. After adjusting for relevant confounders, concurrent antioxidant use with chemotherapy or radiation therapy among 1940 women was associated with increased risk of total mortality (HR: 1.64; 95% CI: 1.01, 2.66) and worsened recurrence-free survival (HR: 1.84; 95% CI: 1.26, 2.68). Overall postdiagnosis supplement use was not associated with breast cancer prognosis. Conclusions Antioxidant use during chemotherapy or radiation therapy was associated with worsened breast cancer prognosis in postmenopausal women. There was no overall association between postdiagnosis supplement use and breast cancer prognosis. Results from our study align with the current recommendation to possibly avoid the use of antioxidants during chemotherapy or radiation therapy.

Background Studies to date have reported several associations between single nucleotide polymorphisms (SNPs) and cancer related fatigue (CRF), but have been limited by small sample sizes, missing adjustment for relevant covariates or multiple testing, as well as varying CRF definitions, i.e. time and method of assessment. This study aimed to validate previously reported associations using the largest independent breast cancer sample to date and to evaluate further functional cytokine variants in relation to total CRF and all relevant CRF subdomains (physical, cognitive, and affective CRF). Method 45 candidate SNPs in inflammatory pathway genes were selected based on previous reports (16 SNPs) or regulatory function (29 SNPs). Breast cancer patients recruited between 2002 and 2005 provided information on CRF at first follow-up (FU1) (N = 1389) and second follow-up (FU2) (N = 950), a median of 6.2 years and 11.7 years respectively after diagnosis. SNP associations were assessed using linear regression models on CRF scores separately for FU1 and FU2. Additionally, patients with persistent fatigue (fatigued at both time-points) were compared to those never fatigued using logistic regression models (N = 684). All analyses were adjusted for relevant covariates. Secondary analyses were conducted for CRF subdomains. Results For total CRF none of the previously reported associations were confirmed after correction for multiple testing. The p-value distribution of all SNPs was not different than the one expected by chance. Analyses of CRF subdomains yielded a significant association between TNF-α rs3093662 and persistent physical CRF (Odds Ratio (OR) = 3.23, 95% Confidence Interval (CI) = 1.71–6.10, p = 0.0003). Conclusion We were unable to confirm previously reported findings, suggesting that individual SNPs are unlikely to be of clinical utility. Further investigations in well powered studies are warranted, which consider genetic heterogeneity according to subdomains of CRF.

Background and objectives Within the German National Cohort (GNC) 100,000 adult women in Germany will be comprehensively interviewed and examined. While women’s health is addressed in the basic interview, direct detection of cervicovaginal microbial colonisation or infection is not part of the examination protocol. In a pilot project the feasibility of female study participants of the GNC collecting a cervicovaginal lavage at home without having to involve a gynecologist or other medical personnel was thus investigated. The ability of the procedure to detect vaginal microbes and conditions including human papillomavirus (HPV), Chlamydia trachomatis and bacterial vaginosis (BV) were also explored. Methods This cross-sectional study was conducted in two study centers (Hamburg and Hanover) of the GNC during Pretest 2 in 2012 as an add-on module to the main program of the National Cohort. Participants were randomly selected through the population registration office. After providing written informed consent at the study center, participants self-collected a cervicovaginal lavage (Delphi Screener™) at home following written instructions. Participants mailed samples and acceptability questionnaires to the laboratory and the study center, respectively. Acceptability of self-sampling was categorized as consent, partial consent and rejection. The samples were analyzed by multiplex HPV genotyping for the presence of 27 mucosal HPV subtypes. To detect other pathogens “Sexually Transmitted Infection Profiling” (STIP) was used, a novel multiplex polymerase chain reaction (PCR) for various vaginally occurring pathogens/conditions coupled with subsequent bead-based Luminex® hybridization. Human beta-globin and DNA polymerase alpha (PolA) sequences were used as positive controls for the detection of human DNA during HPV detection and STIP, respectively. Results The participation based on the proportion of all women in Pretest 2 who could take part in the add-on Pretest 2 was 67.3 % (109 out of 162). The age of participants ranged from 20 to 69 years. The self-reported median duration of the collection of the lavage was 5 min. Analysis of the questionnaires (n = 108) revealed that the self-sampling of a cervicovaginal lavage was acceptable to 98 % of women (106 out of 108), and considered to be easy by 89 % (96 out of 108) as well as user-friendly by 96 % of the women (104 out of 108). Human beta-globin and PolA as markers for human DNA and sample quality were detected in all samples analyzed while HPV as a marker for pathogen detectability was identified in 18 out of 109 samples. Of the 107 samples tested with STIP as a second marker for pathogen detectability, 5 samples were excluded from statistical analyses on bacterial colonization because of signs in the laboratory results of the use of antibiotics. For the computation of the possible occurrence of bacterial vaginosis and candidiasis 7 and 8 samples, respectively, were excluded because of low signal intensities resulting in an evaluation of 95 or 94 samples, respectively. Ureaplasma parvum was detected in 22 out of 102 samples, BV in 14 out of 95 samples and candidiasis in 13 out of 94 samples. Chlamydia trachomatis was not detected in any sample. Conclusion The feasibility study on cervicovaginal self-sampling indicates that this form of biosampling was very well accepted within the framework of the GNC and feasible in terms of pathogen detection. Its further application in the GNC would allow investigation of transience and persistence, or long-term effects of vaginal (co)infections and colonization.

BACKGROUND: We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders. METHODS: We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models. RESULTS: Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ(2), p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed. CONCLUSIONS: The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.

Contains fulltext : 136562.pdf (Publisher’s version ) (Closed access) BACKGROUND: Inconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking. METHODS: We used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50-74 and diagnosed with invasive tumours 2001-2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed. RESULTS: Overall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93-1.64, and HR 1.29, 95% CI 0.95-1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13-2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60-1.98; Pheterogeneity=0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02-3.65, and HR 2.08, 95% CI 1.40-3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22-10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (/=25 kg/m(2): HR 0.94, 95% CI 0.38-2.36; Pheterogeneity=0.04). CONCLUSION: The harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.

Objective: To evaluate the effect of the Quality assured Mamma Diagnostic programme (QuaMaDi) introduced in 2001 on breast cancer and mortality on a population basis. QuaMaDi provides a standardized diagnostic process for symptomatic or at risk women of all ages. The process includes independent double-reading of mammograms, additional ultrasound, and if suspicious an expert reading and assessment. We tested the hypothesis that QuaMaDi has influenced breast cancer epidemiology and survival positively. Methods: The QuaMaDi cohort of breast cancer patients, diagnosed within the programme between 2001 and 2007, was linked to the cancer registry dataset of all breast cancer cases in Schleswig-Holstein, Germany. By this record-linkage procedure participants of QuaMaDi could be marked in the cancer registry data. Overall survival rates of 3096 patients diagnosed within QuaMaDi were compared to 5417 patients diagnosed outside QuaMaDi, matched by year of diagnosis, using multivariate Cox proportional hazard models. Results: Crude hazard ratio for overall survival was HR 0.43 (95% CI 0.35–0.52) for breast cancer cases detected inside QuaMaDi versus those diagnosed outside the programme. After stepwise adjustment for age, grading, histology, treatment, and tumour stage, the survival advantage in QuaMaDi diagnosed breast cancer patients was still statistically significant (HR 0.78, 95% CI 0.64–0.96). Conclusion: Evidence is provided that the QuaMaDi programme has a beneficial impact on the first 5-year overall survival rate after breast cancer beyond a favourable tumour stage distribution. Thus, we conclude that QuaMaDi contributes to improved health care for women, who are not eligible for mammography screening.

Background:The use of herbal preparations (HEP) to alleviate climacteric disorders is expected to increase as women seek alternatives to menopausal hormone therapy to avoid the associated breast cancer risk. Data are sparse on the long-term effects of HEP containing phytoestrogens and black cohosh on breast cancer risk. Methods: Within a German case-control study, associations between patterns of HEP use and incident breast cancer were investigated in 10,121 postmenopausal women (3,464 cases, 6,657 controls). Information on HEP use was collected in face-to-face interviews supported by a list of brand names. Multivariate logistic and polytomous regression analyses were done. Findings: Ever use of HEP (9.9%) was inversely associated with invasive breast cancer [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.63-0.87] in a dose-dependent manner (OR, 0.96 per year of use; P = 0.03). Classes of HEP did not differ significantly (Pheterogeneity = 0.81). Risks for invasive ductal (OR, 0.72; 95% CI, 0.60-0.87) and combined lobular/mixed/tubular tumors (OR, 0.76; 95% CI, 0.58-1.01) were similarly reduced by any HEP use but not for in situ carcinomas (1.34; 95% CI, 0.86-2.09). There were no substantial differences in associations of HEP use by estrogen receptor status (ER+ OR, 0.74; 95% CI, 0.62-0.89; ER− OR, 0.68, 95% CI, 0.50-0.93) and progesterone receptor status of the tumor. Interpretation: Our findings support the hypothesis that HEP use protects from invasive breast cancer in postmenopausal women. Among conceivable modes of action, those independent of estrogen receptor–mediated pathways seem to be involved (i.e., cytotoxicity, apoptosis). (Cancer Epidemiol Biomarkers Prev 2009;18(8):2207–13)

Summary Objectives: Epidemiological evidence suggests an inverse association between physical activity (PA) and postmenopausal breast cancer risk. Breast cancer is a heterogeneous disease, influenced by reproductive factors, lifestyle pattern, and predispositions. We investigated whether these risk factors modify the effect of PA on breast cancer risk. Methods: We analyzed data from 2004 hormone-receptor-positive postmenopausal breast cancer cases and 6569 controls from the population-based MARIE study conducted 2002–2005 in Germany. Interaction was statistically tested using adjusted unconditional logistic regression models. Results: The inverse association between leisure-time PA and risk of postmenopausal hormone-receptor-positive breast cancer was not heterogeneous by family history of breast cancer or by hormone therapy. PA showed a significant interaction with benign breast diseases (p = 0.023) and with breastfeeding (p = 0.045) but not with parity (p = 0.94), with clear risk reductions only for women who ever had breastfed or who ever had a benign breast disease (among ever breastfed: odds ratio = 0.63; 95% confidence interval = (0.52, 0.77), highest vs. lowest PA quartile). Interaction with BMI was weak (p = 0.053). Conclusions: Breastfeeding and benign breast diseases modified the effect of PA on postmenopausal breast cancer risk. If other studies find similar modifications, increasing knowledge about these risk factors may contribute to a better understanding of the mode of action of PA on breast cancer risk. For women who are at higher risk for breast cancer due to family history or due to hormone therapy use, it is encouraging that they might lower their risk by being physically active.

Physical activity (PA) has been inversely associated with postmenopausal breast cancer risk. However, it is unclear how and in which life periods PA may be effective to reduce breast cancer risk. Moreover, the evidence is still not judged as ‘convincing’ as there is some heterogeneity among study results. Most studies regarded breast cancer as a single disease, at best separated by menopausal status. Yet, breast cancers are heterogeneous and likely have different etiologies. Therefore, we analyzed the association of PA with different breast cancer subtypes in 3,414 postmenopausal cases and 6,569 controls from a case-control study on breast cancer conducted 2002-2005 in Germany (MARIE study). PA in the age periods 30-49 and 50+ years was assessed, including leisure-time PA (sports, cycling, walking) and non-recreational PA (occupational and household activities). There was a significant protective effect of leisure-time PA for ER+/PR+ carcinomas (adjusted odds ratio = 0.71, 95% confidence interval: 0.60, 0.85; trend P = 0.0001), but no effect for ER-/PR- carcinomas. Moreover, looking at physical activity pattern over time, the effect of PA after menopause on reducing breast cancer risk was more pronounced than the effect of PA before menopause. Overall, effects of PA were independent from adult weight gain, body mass index, and energy intake. These findings suggest that leisure-time PA after menopause may reduce postmenopausal breast cancer risk at least in part via hormonal pathways and not solely by changing body composition. Inactive postmenopausal women should be encouraged to become physically active even later in life. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3402–10)

Cohort studies of breast cancer (BC) patients, but not of disease-free women at inclusion, have found menopausal hormone therapy (MHT) to be associated with decreased BC specific mortality (BCM). Here, the German population-based MARIEplus BC cohort was analyzed to further elucidate associations of prediagnostic MHT with BCM (and modification by tumor characteristics), recurrence, and secondarily with other cause and overall mortality. Enrolled 2002-2005, incident invasive BC cases (N = 3,321) were followed up for a median of 6.1 years. Cox proportional hazards models adjusted for tumor characteristics, mammography and lifestyle were applied. Compared with never users of MHT, current users at date of diagnosis had significantly lower BCM (Hazard ratio (HR) 0.72, 95% CI 0.53-0.97) and risk of recurrence (HR 0.61, 95% CI 0.46-0.82). The MHT related reduced BCM was confined to patients with low grade tumors (HR 0.44, 95% CI 0.28-0.70; phet = 0.01) and not modified by estrogen receptor or nodal status. BCM decreased with MHT duration in current and increased in past users (phet = 0.015). Mortality due to causes other than BC and overall mortality were also reduced in current MHT users (HR 0.51, 95% CI 0.32-0.81, HR 0.66, 95% CI 0.52-0.86, respectively). Favorable tumor characteristics and mammographic surveillance could not fully explain associations of current MHT use with BCM and recurrence risk. Thus, the study contributes to the evidence that prediagnostic MHT does not have a negative impact on prognosis after BC. The restriction of a reduced BCM to low grade tumors should be confirmed in independent studies.

HINTERGRUND: Die Inzidenz akuter respiratorischer Atemwegs- (ARE) und gastrointestinaler (GIE) Erkrankungen ist schwierig zu erfassen, da Krankheitsepisoden häufig auftreten und diese überwiegend einen kurzen und leichten Verlauf haben. Retrospektive Befragungen sind daher oft anfällig für recall bias, während bei einem prospektiven Vorgehen von den Teilnehmern eine große Disziplin über einen längeren Zeitraum gefordert ist. Web-basierte Fragebögen (WF) erlauben die Integration eines Erinnerungssystems mit kurzen Intervallen und sind potentiell gut geeignet, um häufig auftretende, akute Infektionen über einen längeren Zeitraum zu erfassen. Wir untersuchten, ob Probanden im Rahmen der Nationalen Kohorte (NAKO) bereit und in der Lage sind, ARE- und GIE-Symptome zu erfassen, indem sie über wöchentlich versandte Erinnerungs-E-Mails einen Link zu einem Online-Fragebogen zugeschickt bekommen. MATERIAL UND METHODEN: In den Studienzentren Hamburg und Bremen wurden Teilnehmer des 1. Pretests (09–11/2011) eingeladen, zusätzlich an der Machbarkeitsstudie zum WF teilzunehmen. Jeden Montag erhielten die Teilnehmer eine E-Mail mit einem Link zum WF, in dem sie nach ARE- oder GIE -Symptomen in den vorangegangenen 7 Tagen gefragt wurden. Die Studie wurde von Februar bis Mitte Juli 2012 durchgeführt. Wir untersuchten den Anteil der Teilnehmer insgesamt, die wöchentliche Teilnahme, die wöchentlichen Rückmeldungen/Teilnehmer und berechneten Inzidenzen für ARE, Influenza-ähnliche Erkrankung (ILI) und GIE. ERGEBNISSE: Von 200 Teilnehmern des Pretests erfüllten 171 (86 %) die Voraussetzungen (Zugang zu internetfähigem PC mit funktionierender Email Adresse) für die Teilnahme an der Machbarkeitsstudie. Von diesen 171 Teilnehmern stimmten 167 (98 %) der Teilnahme zu. Teilnehmer waren etwas jünger als Nichtteilnehmer und besser gebildet. Der Zugang zum Internet nahm mit zunehmendem Alter ab. Fünf Teilnehmer (3 %) hatten keine funktionierende E-Mail-Adresse, 18 (11 %) antworteten nicht, 144 (86 %) antworteten mindestens einmal während der gesamten Studie (23 Wochen). Die wöchentlichen Rückmeldungsraten variierten zwischen 62 % und 81 %, der Median betrug 74 % (Interquartil-Bereich 71–77 %). Der Median für die Anzahl der Rückmeldungen/Teilnehmer lag bei 20 (Interquartil-Bereich 14–22; Spannweite 1–23). Über 90 % der Teilnehmer meldeten sich innerhalb der ersten 3 Tage zurück. Die mittlere Inzidenz für ARE und ILI betrug 12 % und 0,49 %, für GIE 3,0 %. SCHLUSSFOLGERUNG: Der Einsatz von WF in der NAKO erscheint gut durchführbar, die Anzahl der Studienteilnehmer mit Internetanschluss war hoch, es traten keine größeren technischen Probleme in der Durchführung auf. Die Teilnahme blieb während der 6-monatigen Studie hoch, die Anzahl von Ausfällen gering. Die Teilnehmer an der Machbarkeitsstudie waren jünger und besser gebildet als Nichtteilnehmer, daher muss ein möglicher selection bias berücksichtigt werden, wenn es um die Übertragbarkeit der Ergebnisse auf die Allgemeinbevölkerung geht. BACKGROUND: Incidence of acute respiratory infections (ARI) and gastrointestinal infections (GII) are difficult to assess due to high frequency episodes, limited severity and short duration. Retrospective assessments therefore are particularly prone to recall bias, while prospective assessment with conventional questionnaires requires high discipline from participants which is difficult to maintain over longer time periods. Web-based questionnaires (WQ) allow integration of a recall system and thus carry the potential to prospectively capture acute infections. We investigated the feasibility of a weekly WQ assessing symptoms of ARI and GII among participants of the German National Cohort (GNC). MATERIAL AND METHODS: In the study centres Hamburg and Bremen of the GNC participants of the Pretest 1 phase (September to November 2011) were invited to additionally take part in this feasibility study testing the WQ. Every Monday participants received an e-mail, containing a link to the WQ, asking for occurrence of ARI or GII symptoms during the past 7 days. The study took place from the beginning of February until mid-July 2012. We calculated the overall proportion of participation, weekly participation and the number of weekly reports per participant and we estimated incidences of ARI, ILI and GII. RESULTS: Of 200 Pretest 1 participants 171 (86 %) reported having an email address and thus were eligible for the web-based study. A total of 167 (98 %) agreed to participate. Participants of the web-based study were younger and better educated than non-participants. Access to Internet decreased with increasing age. Of the 167 participants in the feasibility study, 144 (86 %) responded at least once during the study period of 23 weeks, 5 persons (3 %) had non-functioning email addresses and 18 (11 %) did not respond at all. The weekly response varied between 62 % and 81 %, the median was 74 % (IQR: 71–77 %). Weekly median reports per person were 20 (IQR: 14–22; range 1–23). More than 90 % of participants responded during the first 3 days. The following mean incidence rates were found: ARI, 12 %; ILI, 0.49 %; and GII, 3 %. CONCLUSION: Use of WQ in prospective studies seems well possible, as Internet access is frequent among study participants and major technical problems did not occur. We observed high participation during the study period of 6 months and low drop out numbers. Participants of the web-based study were slightly younger and better educated than non-participants, so selection bias is possible and must be kept in mind when discussing generalizability of the results.

Cats and dogs live in more than 20 % of German households and the contact between these pets and their owners can be very close. Therefore, a transmission of zoonotic pathogens may occur. To investigate whether zoonotic research questions can be examined in the context of population-based studies like the German National Cohort (GNC), two studies on different study populations were conducted as part of the feasibility tests of the GNC. The aim of the first study was to quantify the actual exposure of participants of the GNC to cats and dogs. In the second study summarised here the feasibility of the sampling of cats and dogs by their owners was tested. To quantify the exposure of participants of the GNC to cats and dogs 744 study participants of the Pretests of the GNC were asked whether they had contact with animals. Currently 10 % have a dog and 14 % have a cat in their household. These figures confirm that a large proportion of the German population has contact with pets and that there is a need for further zoonoses research. To establish the collection of biological samples from cats and dogs in the context of large-scale population-based studies feasible methods are needed. Therefore, a study was conducted to test whether pet owners can take samples from their cats and dogs and whether the quality of these samples is comparable to samples taken by a qualified veterinarian. A total of 82 dog and 18 cat owners were recruited in two veterinary practices in Hannover and the Clinic for Small Animals at the University of Veterinary Medicine in Hannover. Sampling instructions and sample material for nasal and buccal swabs, faecal samples and, in the case of cat owners, a brush for fur samples, were given to the pet owners. The pet owners were asked to take the samples from their pets at home and to send the samples by surface mail. Swab samples were cultured and bacterial growth was quantified independent of bacterial species. The growth of Gram-positive and Gram-negative bacteria from samples taken by the veterinarian and the pet owners were compared. For Gram-positive bacteria the agreement of laboratory results was 71 % for nasal swabs and 78 % for oral swabs while for Gram-negative bacteria the agreement of laboratory results was 55 % for nasal swabs and 87 % for oral swabs. In conclusion it has been shown that participants of the GNC are exposed to cats and dogs and that the sampling of cats and dogs by their owners is a feasible method which can be a useful tool for zoonoses research in population-based studies.

BACKGROUND/OBJECTIVES: The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called “ID Screen”) for feasibility and validity. METHODS: From August–November 2011, 435 participants between the ages of 20–69 completed the ID Screen. All subjects had been recruited via a random sample from the local residents’ registration offices by 4 of the 18 participating study centers. The questionnaire encompasses 77 variables in six sections assessing items such as 12-month prevalence of infections, cumulative prevalence of infectious diseases, visit of health care facilities and vaccination. The feasibility was amongst others evaluated by assessing the completeness and comprehensiveness of the questionnaire. To assess the questionnaires ability to measure “immune status” and “susceptibility to infections”, multivariate analysis was used. RESULTS: The overall practicability was good and most items were well understood, demonstrated by 5 % of missing values. However, direct comparison of the items 12-month prevalence and lifetime prevalence of nephritis/pyelitis showed poor agreement and thereby poor understanding by 80 % of the participants, illustrating the necessity for a clear, lay person appropriate description of rare diseases to increase comprehensibility. The questionnaire will be used to support the assessment of immune dysfunction and frequency of infection. An analysis of these constructs in an exploratory factor analysis revealed limited applicability due to low interitem correlation (Cronbach’s α

HINTERGRUND: Daten über den Impfstatus von Teilnehmern in epidemiologischen Studien werden immer dann benötigt, wenn Infektionen oder Immunität als mögliche Exposition oder Outcome betrachtet werden. Wir haben daher die Akzeptanz und Machbarkeit der Impfdatenerhebung durch Erfassung von Impfpässen im Rahmen des Pretest 2 der Nationalen Kohorte untersucht. METHODEN: Die Studie wurde in 3 Studienzentren (Bremen, n = 73; Hamburg, n = 200; Hannover, n = 193) durchgeführt. Um zu testen, ob eine zusätzliche Erinnerung die Bereitstellung der Impfpässe positiv beeinflusst, wurden Personen, die der Teilnahme an Pretest 2 der Nationalen Kohorte zustimmten, einer von drei verschiedenen Erinnerungsgruppen (IG) zugeteilt. Je ein Drittel der Teilnehmer erhielt entweder keine weitere Erinnerung (IG1), eine Erinnerungskarte zusammen mit der Terminbestätigung (IG2) oder eine Erinnerungskarte separat 4 Tage vor dem Untersuchungstermin (IG3). Im Studienzentrum wurden die mitgebrachten Impfpässe unter einem Pseudonym gescannt oder kopiert und in eine Datenbank übertragen. Teilnehmer wurden außerdem gebeten, einen kurzen Fragebogen zur Vollständigkeit der vorgelegten Impfdaten selbstständig auszufüllen. Die Studienteilnehmer in Hannover wurden zusätzlich um das Einverständnis gebeten, Impfdaten über die Hausärzte erheben zu dürfen. Darüber hinaus haben wir die Daten zu Influenzaimpfungen aus den Impfpässen mit den von den Pretest-2-Teilnehmern erinnerten Angaben zu erhaltenen Influenzaimpfungen aus einem Selbstausfüller (ID-Screen) verglichen. ERGEBNISSE: Aufgrund unterschiedlicher Startzeitpunkte der Studie wurde das Erinnerungsverfahren nur in den Studienzentren Hamburg und Hannover wie vorgesehen umgesetzt. In Hamburg wurden signifikant mehr Impfpässe in der Erinnerungsgruppe mit einer separat versendeten Erinnerungskarte 4 Tage vor dem Untersuchungstermin (IG3) mitgebracht, verglichen mit IG1 und IG2 (p = 0,04). In Hannover wurden dagegen die meisten Impfpässe von denjenigen vorgelegt, die die Erinnerungskarte zusammen mit der Terminbestätigung erhielten. Das Versenden einer Erinnerungskarte hat sich, unabhängig davon, ob sie zusammen mit der Terminbestätigung oder separat übermittelt wurde, positiv, jedoch nicht signifikant, auf das Mitbringen der Impfausweise ausgewirkt: Mit Erinnerungskarte haben 89 % (185/209) der Teilnehmer Impfpässe vorgelegt, ohne Erinnerungskarte 81 % (84/104) der Teilnehmer (p = 0,06). Der Datenerhebung über den Hausarzt stimmten 62 % (120/193) aller Pretest-2-Teilnehmer in Hannover zu. Von den 114 angeschriebenen Hausärzten haben 49 Ärzte (43 %) Impfdaten geschickt. 360 Impfpässe mit 5065 Einträgen wurden in eine Impfdatenbank eingegeben. Von diesen sind 4830 (95 %) verwertbar. Die Impfeinträge umfassen den Zeitraum von 1946 bis 2012. Der Vergleich von in den Impfpässen dokumentierten Influenzaimpfungen mit den im Selbstausfüller erinnerten Angaben zeigte eine Übereinstimmung der Daten in 46 % (84/184) der Fälle (Kappa = 0,48). Influenzaimpfungen wurden in 4 % der Fragebögen (7/170) untererfasst. SCHLUSSFOLGERUNGEN: Die hohe Bereitschaft und Zuverlässigkeit der Probanden, ihre Impfpässe vorzulegen, zeigte, dass auf diese Weise eine verlässliche Impfdokumentation im Rahmen der Nationalen Kohorte erfolgen und somit auch in größerem Umfang empfohlen werden kann. Auch erscheint die zusätzliche Validierung über die hausärztliche Dokumentation für über ein Viertel aller Probanden möglich. Um an das Mitbringen der Impfpässe zu erinnern, reicht ein ergänzender Satz in der Terminbestätigung, der standardmäßig eine farbige Erinnerungskarte beigelegt werden sollte. BACKGROUND: Data about the vaccination status of participants are required in epidemiological cohort studies whenever infection or immunity is considered as potential exposure or outcome. Within Pretest 2 of the German National Cohort (GNC) we therefore investigated the acceptance and feasibility of extracting vaccination status from vaccination certificates provided by the participants of the study. METHODS: This study was conducted in three study centers (Bremen, n = 73; Hamburg, n = 200; Hannover, n = 193). In order to test if an additional reminder would prevent participants from forgetting their vaccination certificates at home persons willing to participate in Pretest 2 were randomly assigned to one of three invitation groups (IG). About one third of the participants received either no further reminder (IG1), a reminder card together with the appointment letter (IG2) or a separate reminder card 4 days before the appointment (IG3). At the study center, vaccination data were scanned or copied and entered into a database using a unique identification number. Participants were also asked to fill in a short questionnaire to assess the completeness of the provided vaccination data. Additionally, in one of the three participating study centers, general practitioners (GP) were asked to provide vaccination data from their records following respective participants’ consent. Finally, we compared the influenza data from the vaccination certificates with the influenza data obtained from participants in Pretest 2 by use of a self-administered questionnaire (ID-Screen). RESULTS: Due to different starting dates of the study the intended reminder procedure was implemented only in Hamburg and Hannover. In Hamburg, significantly more vaccination certificates were submitted by the group which received the reminder card separately 4 days before the examination (IG3) compared to IG1 and IG2 (p = 0.04). In Hannover, in contrast, most vaccination certificates were brought by those who received the reminder card together with the appointment letter. Overall, the use of a reminder card had a positive but not significant effect as 89 % (185/209) of participants who received the reminder card submitted vaccination data versus 81 % (84/104) of participants who did not receive any reminder card (p = 0.06). Of all Pretest 2 participants in Hannover, 62 % (120/193) gave written consent for data collection by the GPs. In total, 114 practices were contacted of which 49 (43 %) sent vaccination data. All in all, 360 vaccination certificates with 5065 documented vaccinations were entered into a database, of which 4830 (95 %) were valid for analysis covering a period from 1946 to 2012. The comparison of influenza vaccination data from vaccination certificates to the remembered data from a self-completed questionnaire showed an agreement of data in 46 % (84/184) of cases (Kappa = 0.48). Influenza vaccinations were underreported in 4 % (7/170) of self-completed questionnaires. CONCLUSION: The reliable documentation of vaccinations within the context of the GNC proved to be feasible and thus recommendable at a large scale within the GNC as participants showed high willingness and compliance in providing available vaccination documents. An additional validation by means of documents provided by physicians seems to be possible for more than a quarter of participants. In order to maximize the likelyhood of participants’ of bringing their vaccination certificates it would be sufficient to send a reminder card together with the appointment letter.

Response rates in epidemiologic studies vary widely. This study examines response rates of potential study participants according to foreign versus German background and investigates effects of recruitment strategies. Response rates and characteristics of recruitment procedures from feasibility studies for a large cohort study conducted in 2011 were analyzed. Among 1,235 participants the proportion of recruited individuals with a foreign background was 17.3 % (95 % confidence interval 15.3–19.5 %), significantly lower than in the sampling frame (23.1 %). The difference between observed and expected proportion was high among individuals with Turkish background and smaller among ethnic Germans from the Former Soviet Union and other foreign background groups. Common recruitment strategies to increase the response had positive effects in all groups. For the planned recruitment strategy in the forthcoming German National Cohort, we estimate an overall response of approximately 50 %. Individuals with Turkish background may need particular efforts to be adequately represented in a population-based cohort in Germany. Other foreign background groups are relatively well represented using standard procedures. An adequate response can be obtained under carefully planned recruitment strategies.

We previously reported that lower post-diagnostic circulating 25-hydroxyvitamin D [25(OH)D] concentrations were associated with higher risk of overall mortality and distant disease in stage I-IV postmenopausal breast cancer survivors. This association was now re-examined in an extended dataset to investigate potential effect modification by tumor characteristics and lifestyle factors. A prospective cohort study was conducted in Germany including 2,177 incident stage I-IV postmenopausal breast cancer patients aged 50-74 years. Patients were diagnosed between 2001 and 2005 and median follow-up time was 5.3 years. Cox proportional hazards models were stratified by age at diagnosis, study center and season of blood collection and adjusted for other prognostic factors. A meta-analysis of studies on circulating 25(OH)D and mortality in breast cancer patients was performed to summarize evidence. Lower concentrations of 25(OH)D were significantly associated with higher risk of overall mortality [hazard ratio (HR) lowest vs. highest tertile = 1.86; 95% confidence interval (CI): 1.22, 2.82; p-trend = 0.002] and distant disease (HR = 1.76; 95% CI: 1.24, 2.49; p-trend = 0.003) in stage I-IIIa but not in stage IIIb-IV breast cancer patients. No significant interaction by lifestyle factors was observed (all p-interaction 0.05). The meta-analysis yielded significant associations with overall and breast cancer-specific mortality (lowest vs. highest quantile: HR = 1.52; 95% CI: 1.22, 1.88 and HR = 1.74; 95% CI: 1.23, 2.40, respectively). In conclusion, post-diagnostic circulating 25(OH)D concentrations were associated with overall mortality and distant disease in stage I-IIIa postmenopausal breast cancer patients. This association was not strongly modified by lifestyle factors.

Item does not contain fulltext PURPOSE: Comorbid conditions have become increasingly relevant for breast cancer care given the large numbers of long-term survivors. Our aim was to identify potential determinants associated with the development of comorbidities after breast cancer. METHODS: Self-reported comorbidities and lifestyle were assessed at recruitment and after a median follow up of 69.4 months from diagnosis in a population-based cohort of breast cancer cases aged 50 to 74 years at diagnosis (MARIEplus study). Tumor and therapy data were extracted from medical records. Determinants potentially associated with incident diagnoses of hypertension, cardiovascular diseases (CVD), and osteoporosis were assessed using multivariable Cox proportional hazard regression models. RESULTS: Follow-up interview was completed by 2,542 women (76.4 % of eligible patients). A diagnosis of hypertension was significantly associated with age, higher education (hazard ratio (HR) 0.54, CI 0.37-0.79), baseline body mass index (BMI; >/=30 kg/m(2); HR, 1.90; CI, 1.24-2.90), and trastuzumab medication (HR, 2.16; CI, 1.09-4.33). An increased risk for CVD was associated with age, BMI, and intake of aromatase inhibitors (AI; HR, 1.42; CI, 1.09-1.84). Risk of osteoporosis was also positively associated with AI treatment (HR, 2.15; CI, 1.64-2.82) but inversely associated with a higher BMI (>/=30 kg/m(2); HR, 0.50; CI, 0.31-0.79). CONCLUSION: In breast cancer survivors, treatment with AI constituted a risk factor for incident CVD and osteoporosis. Besides known risk factors, patients who were treated with trastuzumab may have an increased risk for hypertension. IMPLICATIONS FOR CANCER SURVIVORS: Reducing overweight and regular sport/cycling activities may help to prevent CVD after breast cancer. Patients should be monitored for risk factors and advised on possible cardiac side effects of AI and trastuzumab.

Contains fulltext : 118401.pdf (Publisher’s version ) (Open Access) Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 x 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 x 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of /= 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 x 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

Contains fulltext : 125676.pdf (Publisher’s version ) (Open Access) Lipid-lowering drugs are used for the prevention of cardiovascular diseases. Statins are the most commonly used lipid-lowering drugs. Evidence from preclinical and observational studies suggests that statins might improve the prognosis of breast cancer patients. We analyzed data from the German MARIEplus study, a large prospective population-based cohort of patients aged 50 and older, who were diagnosed with breast cancer between 2001 and 2005. For overall mortality, breast-cancer specific mortality, and non-breast-cancer mortality, we included 3189 patients with invasive breast cancer stage I-IV, and for recurrence risk 3024 patients with breast cancer stage I-III. We used Cox proportional hazards models to assess the association with self-reported lipid-lowering drug use at recruitment. We stratified by study region, tumor grade, and estrogen/progesterone receptor status, and adjusted for age, tumor size, nodal status, metastases (stage I-IV only), menopausal hormone treatment, mode of detection, radiotherapy, and smoking. Mortality analyses were additionally adjusted for cardiovascular disease, diabetes mellitus and body-mass index. During a median follow-up of 5.3 years, 404 of 3189 stage I-IV patients died, and 286 deaths were attributed to breast cancer. Self-reported use of lipid-lowering drugs was non-significantly associated with increased non-breast cancer mortality (Hazard ratio (HR) 1.49, 95% confidence interval (CI) 0.88-2.52) and increased overall mortality (HR 1.21, 95% CI 0.87-1.69) whereas no association with breast cancer-specific mortality was found (HR 1.04, 0.67-1.60). Restricted to stage I-III breast cancer patients, 387 recurrences occurred during a median follow-up of 5.4 years. We found lipid-lowering drug use to be non-significantly associated with a reduced risk of recurrence (HR 0.83, 95% CI 0.54-1.24) and of breast cancer-specific mortality (HR 0.89, 95% CI 0.52-1.49). Although compatible with previous findings of an improved prognosis associated with statin use, our results do not provide clear supportive evidence for an association with lipid-lowering drug use due to imprecise estimates.

Evidence is emerging that physical activity (PA) may improve overall survival after breast cancer diagnosis. However, the effect of PA on breast cancer recurrence and on cause-specific mortality is less investigated. We assessed the association of pre-diagnosis PA with recurrence, overall and cause-specific survival in a prospective cohort study in Germany including 3,393 non-metastatic breast cancer patients aged 50-74 years. Cox proportional hazards models were calculated adjusted for relevant prognostic factors. During a median follow-up of 5.6 years, 367 patients deceased. Overall mortality was significantly inversely associated with pre-diagnosis recreational PA. However, this effect was mainly attributed to deaths due to causes other than breast cancer. Multiple fractional polynomial analyses yielded a nonlinear association with markedly increased non-breast cancer mortality for women who did not engage in any sports or cycling in the years before the breast cancer diagnosis with a hazard ratio (HR, none vs. any) of 1.71, 95% confidence interval (1.16, 2.52). There were no further risk reductions with increasing activity levels. The association with breast cancer-specific mortality showed a similar dose-response but was far less pronounced with HR (none vs. any) = 1.22 (0.91, 1.64). In contrast, regarding cancer recurrence the dose-response was linear. However, this association was restricted to estrogen/progesterone receptor-negative (ER-/PR-) cases (p interaction = 0.033) with HR (highest vs. no recreational PA) = 0.53 (0.24, 1.16), p trend = 0.0045. Thus, breast cancer patients with a physically inactive lifestyle pre-diagnosis may decease prematurely irrespective of their cancer prognosis. Higher levels of exercise may reduce the risk of recurrence of ER-/PR- breast tumors.

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene–environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10−6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10−4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01–1.16) in nulliparous women and ranged from 1.03 (0.96–1.10) in parous women with one birth to 1.26 (1.16–1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85–0.98) in those with an alcohol intake of, Author Summary Breast cancer involves combined effects of numerous genetic, environmental, and behavioral risk factors that are unique to each individual. High risk genes, such as BRCA1 and BRCA2, account for only a small proportion of disease occurrence. Recent genome-wide research has identified more than 20 common genetic variants, which individually alter breast cancer risk very moderately. We undertook an international collaborative study to determine whether the effect of these genetic variants vary with environmental factors, such as parity, body mass index (BMI), height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, and physical activity, which are known to affect risk of developing breast cancer. Using pooled data from 24 studies of the Breast Cancer Association Consortium (BCAC), we provide first convincing evidence that the breast cancer risk associated with a genetic variant in LSP1 differs with the number of births and that the risk associated with a CASP8 variant is altered by high alcohol consumption. The effect of an additional genetic variant might also be modified by reproductive factors. This knowledge will stimulate new research towards a better understanding of breast cancer development.

Item does not contain fulltext Study results on the association of alcohol consumption with breast cancer survival are inconsistent, partly due to the use of different survival outcomes. We assessed the association of pre-diagnostic alcohol consumption with survival and recurrence in a prospective cohort study in Germany including 2,522 postmenopausal breast cancer patients aged 50-74 years. Patients were diagnosed between 2001 and 2005 and vital status, causes of death, and recurrences were verified through the end of 2009. Cox proportional hazards models were stratified by age at diagnosis and study center and adjusted for relevant prognostic factors. Alcohol consumption was non-linearly associated with increased breast cancer-specific mortality [e.g., >/=12 vs. /=12 vs. /=12 vs. /=12 vs.

Background : The publication of the Women's Health Initiative Study [1] in 2002 and the Million Women Study [31] in 2003 on the association of menopausal hormone therapy (HT) and breast cancer were followed by a decrease in the prescription of HT to menopausal women in western countries. In the following years several papers from different countries reported declines in breast cancer incidence and discuss whether this decline is related to the decreased use of menopausal hormone therapy. Methods : We contribute further data by analysing breast cancer incidence rates from the Hamburg Cancer Registry, Germany, for the time period 1991–2006 and HT use data from a large case–control study conducted in the Hamburg region. At first we determined whether there is a decline in breast cancer incidence in 2002/2003. To find supporting evidence for a causal relationship between breast cancer incidence and use of menopausal hormones we addressed the following issues: The decline in incidence should be more pronounced in the age groups, in which HT is used predominantly, i.e. age group 50–69. The decline in incidence should be most pronounced for breast cancer types more strongly associated with HT, i.e. invasive lobular cancer. Results : We observed a statistical significant decline in incidence of all invasive breast cancer in 2002/2003 in Hamburg. The increase in breast cancer incidence as well as the decline was most pronounced in the age group 50–69. Regarding the histological types of tumours in this age group the decline was only pronounced for invasive lobular cancer. The estimated prevalence of HT indicates a decreasing hormone use starting in 2001/2002. We found a strong decrease in prescriptions for menopausal hormone therapy between 2002 and 2005. Conclusion : In summary, our data add to the evidence of a relation between breast cancer incidence and menopausal hormone use.

Background: Breast cancer is a heterogeneous disease with subtypes that may vary in their etiologies. Menopausal hormone therapy has been associated more strongly with lobular and tubular than ductal histologic types and with tumors that are smaller, hormone receptor–positive, and of lower grade. At the same time, correlations have been observed between histology and clinical characteristics. To identify those tumor subtypes most strongly associated with hormone therapy use, it is necessary to disentangle these interrelationships. Methods: Based on 3,464 postmenopausal breast cancer cases and 6,657 controls from the population-based Mammary carcinoma Risk factor Investigation study, we used polytomous logistic regression to evaluate associations between hormone therapy use and risk of invasive breast cancer subtypes. We assessed variations in risk for selected tumor characteristics among histologic and hormone receptor subtypes, both overall and for specific hormone therapy regimens. Results: Lobular and mixed types showed less variation by prognostic factors than did ductal tumors. Current hormone therapy use had the strongest associations with prognostic variables in estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal tumors and in lobular tumors regardless of ER/PR status, with little effect on ER/PR-negative ductal tumors. The observed associations varied minimally by hormone therapy type or regimen. Conclusion: Current hormone therapy use was associated with more favorable breast cancer characteristics for ductal tumors but had less effect on prognostic characteristics in women with lobular tumors. Both histologic type and estrogen receptor/progesterone receptor status seem to be important in explaining the role of hormone therapy in the etiology of breast cancer subtypes. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1188–96)

In a large population-based case-control study in Germany, including 3,464 breast cancer cases aged 50-74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face-to-face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%-confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55-1.94) and heterogeneous by histological type (p0.01), being more than 2-fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04-1.06) for continuous combined estrogen-progestagen, 1.03 (95% CI, 1.02-1.04) for cyclical EP and 1.01 (95% CI, 1.00-1.03) for estrogen-only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone- or levonorgestrel-derived progestagens than for continuously administered progesterone-derived progestagens (OR, 2.27, 95% CI, 1.98-2.62 vs. 1.47, 95% CI, 1.12-1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose.