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Vivian Langagergaard,1 Jens P Garne,2 Ilse Vejborg,3 Walter Schwartz,4 Martin Bak,5 Anders Lernevall,1 Nikolaj B Mogensen,6 Heidi Larsson,7 Berit Andersen,1 Ellen M Mikkelsen7 1Department of Public Health Programs, Randers Hospital, Randers, Denmark; 2Department of Breast Surgery, Aalborg Hospital, Aalborg, Denmark; 3Diagnostic Imaging Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 4Center of Mammography, 5Department of Pathology, Odense University Hospital, Denmark; 6Department of Radiology, Ringsted Hospital, Ringsted, Denmark; 7Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Abstract: The Danish Quality Database of Mammography Screening (DKMS) was established in 2007, when screening was implemented on a nationwide basis and offered biennially to all Danish women aged 50–69 years. The primary aims of the database are to monitor and evaluate the quality of the screening program and – after years of follow-up – to evaluate the effect of nationwide screening on breast cancer-specific mortality. Here, we describe the database and present results for quality assurance from the first round of national screening. The steering committee for the DKMS defined eleven organizational and clinical quality indicators and standards to monitor the Danish breast cancer screening program. We calculated the relevant proportions and ratios with 95% confidence intervals for each quality indicator. All indicators were assessed on a national and regional level. Of 670,039 women invited for mammography, 518,823 (77.4%) participated. Seventy-one percent of the women received the result of their mammography examination within 10 days of screening, and 3% of the participants were recalled for further investigation. Among all detected cancers, 86% were invasive cancers, and the proportion of women with node negative cancer was 67%. There were 36% women with small cancers, and the ratio of surgery for benign lesions to malignant lesions was 1:6.3. A total of 80% of women with invasive cancers were treated with breast conserving therapy. Screening interval and interval cancers were not relevant in the first round, and data regarding radiation dose were not available at the time of evaluation. Overall, the quality indicators showed satisfactory quality in the first round of national breast cancer screening in Denmark. The DKMS is a potentially valuable tool for improving quality and conducting research in the field of breast cancer screening. Keywords: screening, breast cancer, quality indicators

Lone Winther Lietzen1, Gitte Vrelits Sørensen1, Anne Gulbech Ording1, Jens Peter Garne2, Peer Christiansen3, Mette Nørgaard1, Jacob Jacobsen11Department of Clinical Epidemiology, 2Department of Breast Surgery, Aalborg Hospital, 3Breast and Endocrine Section, Department of Surgery P, Aarhus University Hospital, DenmarkObjective: Breast cancer is the most common cancer among women worldwide. The Nordic countries have relatively high survival, but Denmark has a lower survival than neighboring countries. A breast cancer screening program was introduced in 2007 and 2008 in the northern and central regions of Denmark respectively. We aimed to examine possible changes in survival of Danish breast cancer patients in central and northern Denmark in the period 1998–2009.Materials and methods: From the northern and central Denmark regions, we included all women (n = 13,756) with an incident diagnosis of breast cancer, as recorded in the Danish National Registry of Patients during the period January 1, 1998 through December 31, 2009. We calculated age-stratified survival and used Cox proportional hazard regression to estimate mortality rate ratios (MRRs) for all breast cancer patients.Results: Median age was 62 years (21–102 years). The overall 1-year survival improved steadily over the period from 90.9% in 1998–2000 to 94.4% in 2007–2009, corresponding to a 1-year age adjusted MRR of 0.68 in 2007–2009 compared with the reference period 1998–2000. We estimated the 5-year survival to improve from 70.0% in 1998–2000 to 74.7% in 2007–2009, corresponding to a 5-year age adjusted MRR of 0.82 in 2007–2009 compared with the reference period 1998–2000. For middle-aged women (50–74 years) 1-year survival increased from 92.8% in 1998–2000 to 96.6% in 2008–2009, and 5-year survival was expected to increase from 73.9% in 1998–2000 to 80.2% in 2007–2009. Among younger women (15–49 years) and elderly women (>75 years), 1-year survival and 5-year predicted survival did not change over the two time periods.Conclusion: Survival of breast cancer patients has improved in Denmark over the period 1998–2009, and this change was most distinct in women aged 50–74 years. Survival improved even before the implementation of a formal breast cancer screening program.Keywords: breast neoplasm, mortality, epidemiology, population-based

One hundred and twenty-four patients with palpable tumours underwent sentinel lymph node biopsy (SLNB) and subsequent axillary lymph node dissection. Ultrasound of the axilla was used as part of the diagnostic work-up on all patients and those with lymph node metastasis verified by fine-needle aspiration biopsy (FNAB) were not included. For identifying the SLNs, a combination of Tc-99m-labelled human albumin (Solco-ALBU-RES) and blue dye (Patent Blue V) was used. No lymphoscintigraphy was performed. The SLN was successfully identified in 122 out of 124 (98%) patients and 66 (54%) patients were found to have metastatic involvement of the axillary lymph nodes. In 52 (79%) of these patients, the SLNs were the only nodes involved, 28 (54%) had micrometastasis only. The false-negative rate was 1.5%. This method has proven valid in the staging of the axilla in patients with breast cancer. The advanced techniques of serial sectioning and immunohistochemical staining further improve the diagnostic advantage offered by the SLNB, as it increases the possibility of diagnosing micrometastatic deposits. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer and psychiatric disorders negatively impact work life, both positively associated with unemployment and early retirement. Our purpose was to assess whether being prescribed psychiatric medication, 2-4 yrs prior to a diagnosis of breast cancer, could impact the likelihood of returning to work after cancer therapy. Methods: 16,868 self-supporting women, diagnosed with breast cancer in Denmark from 2000 to 2012, were identified from a population-based clinical database, then cross-referenced to data held for psychiatric medication usage, sociodemographics, and labour-market participation. The association between historic psychiatric medication and return to work was estimated using a modified Poisson regression model. 'Return to work' was defined as being self-supporting one year after diagnosis of breast cancer. Results: 16% of our cohort had used psychiatric medical treatment 2-4 years before their diagnosis. Sixty-three per cent of these individuals had returned to work one year later, compared to 69% of the patient group with no prior history of using psychiatric medication treatments. In the fully adjusted model, prior use of psychiatric medication diminished the likelihood of returning to work one year after cancer diagnosis (RR = 0.91 (0.87-0.94)). High income and older age were positively associated with returning to work; negative correlates included those related to disease severity. Conclusions: Historic use of psychiatric medication provoked a minor, although statistically significant reduction in the resumption of working life one year after a diagnosis of breast cancer. Implications for cancer survivors: Although historic use of psychiatric medication may incur a minor effect on working life, further research is needed on the long-term social consequences for sub-groups.

Background: Gene expression profiles of normal and tumor tissue reflect both differences in biological processes taking place in vivo and differences in response to stress during surgery and sample handling. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing is described in a few studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery., Methods: Three women with primary operable breast cancer underwent in situ biopsies from normal breast and tumor tissue prior to radical mastectomy. Ex vivo biopsies from normal and tumor tissue were collected immediately after surgical excision. The putative effects on gene expression of malignancy (tumor versus normal), surgical manipulation (post- versus pre-surgical) and interaction between the two (differences in effect of surgical manipulation on tumor and normal samples) were investigated simultaneously by Generalized Estimating Equation (GEE) analysis in this self-matched study., Results: Gene set enrichment analysis (GSEA) demonstrates a marked difference in effect of surgical manipulation on tumor compared to normal tissue. Interestingly, a large proportion of pathways affected by ischemia especially in tumor tissue are pathways considered to be specifically up regulated in tumor tissue compared to normal., Conclusion: The results of this study suggest that a large contribution to this differential expression originates from altered response to stress in tumor cells rather than merely representing in vivo differences. It is important to bear this in mind when using gene-expression analysis to deduce biological function, and when collecting material for gene expression profiling.

Background: A breast cancer diagnosis affects an individual's affiliation to labour market, but the long-term consequences of breast cancer on income in a Danish setting have not been examined. The present study investigated whether breast cancer affected future income among Danish women that participated in the work force. We also examined the roles of sociodemographic factors and prior psychiatric medical treatment., Methods: This registry-based cohort study was based on information retrieved from linked Danish nationwide registries. We compared the incomes of 13,101 women (aged 30-59 years) diagnosed with breast cancer (exposed) to those of 60,819 women without breast cancer (unexposed). Changes in income were examined during a 10-year follow-up; for each follow-up year, we calculated the mean annual income and the relative change compared to the income earned one year prior to diagnosis. Expected changes in Danish female income, according to calendar year and age, were estimated based on information from Statistics Denmark. For exposed and unexposed groups, the observed income changes were dichotomized to those above and those below the expected change in income in the Danish female population. We examined the impact of breast cancer on income each year of follow-up with logistic regression models. Analyses were stratified according to educational level, marital status, and prior psychiatric medical treatment., Results: Breast cancer had a temporary negative effect on income. The effect was largest during the first three years after diagnosis; thereafter, the gap narrowed between exposed and unexposed cohorts. The odds ratio for an increase in income in the cancer cohort compared to the cancer-free cohort was 0.81 (95% CI 0.77-0.84) after three years. After seven years, no significant difference was observed between cohorts. Stratified analyses demonstrated that the negative effect of breast cancer on income lasted longest among women with high educational levels. Being single or having received psychiatric medical treatment increased the chance to experience an increase in income among women with breast cancer., Conclusion: A breast cancer diagnosis led to negative effects on income, which ameliorated over the following seven years. Sociodemographic factors and prior psychiatric medical treatment might influence long-term consequences of breast cancer on income.

Purpose: This study explores the applicability of registry data as a proxy for perceived stress by examining the association between perceived stress measured in health surveys and registry data., Methods: Of 35,700 randomly invited participants from the 2010 Health Survey in the North Denmark Region (age 16-99 years), 21,842 answered 10 items from Cohen's Perceived Stress Scale. Respondents were divided into quartiles based on their stress score. Survey information was individually linked to national registries containing information on prescribed psychiatric medication and consultations with psychologists or psychiatrists from 2009 to 2011., Results: The percentage of persons with prescriptions or consultations was higher (37.6%) in the highest stress score group, compared with the lowest stress score group (7.7%). Odds ratio (95% confidence interval) for the highest score compared with the lowest score was 7.3 (6.5-8.1). Different combinations of treatment showed low sensitivity (8.7%-37.6%), positive predictive value (49.4%-56.8%), and positive agreement (16.2%-42.7%) were found, whereas specificity (88.5%-98.0%) and negative agreement (85.5%-87.2%) were higher. Kappa measure showed slight to fair agreement (0.104-0.285)., Conclusions: Participants reporting high perceived stress were more often prescribed medications and referred for consultations with psychologists or psychiatrists. However, due to low predictive values, registry data may not be suitable as a proxy for perceived stress., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Women with breast cancer often experience distress. This cohort study investigated the prevalence of distress, predictors of distress, and changes in distress during surgical continuity of care for breast cancer (from diagnosis to commencement of adjuvant treatment)., Methods: The participants were 1079 women with breast cancer who were recruited between April 2013 and May 2014 from 11 breast surgery departments in Denmark. Distress was evaluated using the Distress Thermometer (DT) and predictors of distress were assessed with a self-administered questionnaire at the time of diagnosis (T1), at discharge (T2), and by the start of adjuvant treatment or follow-up (T3). Repeated measures ANOVA, simple and multiple linear regression, and mixed effects regression models were used to identify predictors and estimate changes in distress., Results: At T1, 249 (24.3%) women reported no or minimal distress, 298 (29.1%) moderate distress, and 407 (39.8%) severe distress. The mean distress was 5.5 points on the DT, which decreased by 0.70 (95% confidence interval (CI) -0.80, -0.54) points from T1 to T3. Predictors of distress were time since diagnosis, age, prior or concurrent intake of antidepressants or sedative medicine, prior emotional status, children living at home, feelings regarding femininity and attractiveness, and hospital., Conclusions: More than two-thirds of women with breast cancer experienced moderate or severe distress. Mean distress decreased slightly during surgical continuity of care. However, for some women, distress remained unchanged or even worsened. These findings highlight the need to identify the individual women with distress and offer them adequate support and care., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Symptomatic breast cancers may be more aggressive as compared to screen-detected breast cancers. This could favor axillary lymph node dissection (ALND) in patients with symptomatic breast cancer and positive sentinel nodes., Method: We identified 955 patients registered in the Danish Breast Cancer Cooperative Group (DBCG) Database in 2008 - 2010 with micrometastases (773) or isolated tumor cells (ITC) (182) in the sentinel node. Patients were cross-checked in the Danish Quality Database of Mammography Screening and 481 patients were identified as screen-detected cancers. The remaining 474 patients were considered as having symptomatic cancers. Multivariate analyses of the risk of non-sentinel node metastases were performed including known risk factors for non-sentinel node metastases as well as method of detection., Results: 18% of the patients had metastases in non-sentinel nodes. This was evenly distributed between patients with symptomatic and screen-detected cancers; 18.5% vs 17.5% (OR 1.07; 95% CI 0.77-1.49; p = 0.69). In patients with micrometastases 21% had non-sentinel node metastases in the group with symptomatic cancers compared to 19% of patients with screen-detected cancers. This difference was not significant (OR 1.16; 95% CI 0.81-1.65, p = 0.43). Neither the multivariate analysis showed an increased risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected cancers (OR 1.12, CI 0.77-1.62, p = 0.55). In patients with ITCs 8% of patients with symptomatic cancers had non-sentinel node metastases compared to 13% of patients with screen-detected cancers. This difference was not significant (OR 0.58; 95% CI 0.22-1.54, p = 0.27). In the multivariate analysis, the risk of non-sentinel node metastases was still not significantly increased in patients with symptomatic cancers compared to screen-detected cancers (OR 0.45; 95% CI 0.16-1.27, p = 0.13)., Conclusion: We did not find any clinically relevant difference in the risk of non-sentinel node metastases between patients with symptomatic and screen-detected cancers with micrometastases or ITC in the sentinel node.

Purpose: A diagnosis of breast cancer is a key turning point in a woman's life that may lead to her experiencing severe and persistent distress and potentially presaging a psychiatric disorder, such as major depression. In Denmark an increased standardization of care and a short hospital stay policy minimize the time of medical and nursing surveillance. Consequently, there is the potential risk that distress goes unnoticed, and therefore, untreated. Therefore, the purpose of this study was to explore the experience of distress in Danish women taking part in surgical continuity of care for breast cancer., Methods and Sample: A phenomenological-hermeneutic approach inspired by the French philosopher Paul Ricoeur was conducted to explore the experience of distress in relation to surgical treatment and care for breast cancer. Semi-structured interviews were conducted with 12 women who recently had surgery for breast cancer at six departments of breast surgery in Denmark from May 2013 to November 2013., Key Results: The understanding of the experience of distress in the period of surgical continuity of care for breast cancer is augmented and improved through a discussion related to four identified themes: A time of anxiety, loss of identities, being treated as a person and being part of a system, drawing on theory and other research findings., Conclusion: Distress experienced by women in the period following diagnosis arises from multiple sources. Support and care must be based on the woman's individual experience of distress., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to investigate the use of sentinel lymph node dissection (SLND) in the treatment of patients with locally recurrent breast cancer., Methods: A total of 147 patients with locally recurrent breast cancer were included from five different breast surgery departments in Denmark. Data on previous breast and axillary surgery, adjuvant treatment, second operation in the breast and axilla, and lymphoscintigraphy were collected retrospectively from the original patient files., Results: SLND after recurrence (SLNDAR) was successful in 72 of 144 patients (50 %). The detection rate was significantly higher after previous SLND (66 %) compared with previous ALND (34 %) [p = 0.0001]. Thirty-seven patients (51 %) who had previous SLND had a negative sentinel node. These patients could be spared an ALND. Six patients (8 %) who had a previous ALND had a metastatic sentinel node at recurrence; 17 % of patients had a sentinel node located outside the ipsilateral axilla; and eight patients with negative sentinel node at SLNDAR underwent completion ALND. None of these patients had metastases at completion ALND, corresponding to a false negative rate of 0 %., Conclusions: SLNDAR seems to be a feasible procedure in locally recurrent breast cancer and can spare a clinically significant number of patients an unnecessary ALND and the following risk of sequelae. In patients who had previous ALND, SLNDAR identified metastases that would have been overlooked following the current guidelines. A large proportion of patients had aberrant drainage, suggesting a need for lymphoscintigraphy.

Purpose: Women with breast cancer often experience significant distress. Currently, there are no questionnaires aimed at identifying women's unique and possible changing indicators for distress in surgical continuity of care for breast cancer. We developed and tested three questionnaires specifically for this use., Methods and Sample: We first searched PubMed, CINAHL and PsycINFO to retrieve information on previously described indicators. Next, we conducted a focus group interview with 6 specialised nurses, who have extensive experience about consequences of breast cancer for women in surgical continuity of care. The questionnaire was tested on 18 women scheduled for breast cancer surgery. Subsequently, the women were debriefed to gain knowledge about comprehensibility, readability and relevance of items, and the time needed to complete the questionnaire. After adjustment, the questionnaires were field-tested concomitantly with a clinical study, which both consisted of a survey and an interview study., Key Results: Three multi-item questionnaires were developed specific to different time points in surgical continuity of care. The questionnaires share a core of statements divided into seven sub-scales: emotional and physical situation, social condition, sexuality, body image, religion and organisational factors. Besides the core of statements, each questionnaire has different statements depending on the time point of surgical continuity of care when it was to be responded to., Conclusion: The questionnaires contain comprehensive items that can identify indicators for distress in individual women taking part in surgical continuity of care. The items were understandable and the time used for filling in the questionnaires was reasonable., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: It remains unknown whether incident chronic diseases are more often fatal among breast cancer survivors than among women free of breast cancer., Methods: We conducted a nationwide matched cohort study of all Danish breast cancer patients diagnosed between 1994 and 2007, who survived for five years. We compared their long-term mortality with five times as many women from the general population without breast cancer, matched on age. We used time-varying methods to compute mortality rate ratios (MRRs) for incident diseases included in the Charlson Comorbidity Index (CCI)., Results: One third of five-year breast cancer survivors developed incident diseases during 14 years of follow-up, with about the same incidence as women without breast cancer. Mortality associated with any incident disease was similar among breast cancer survivors (MRR = 7.1, 95% confidence interval (CI): 6.7, 7.4) and comparison women (MRR = 7.5, 95% CI: 7.3, 7.7). Among breast cancer patients, relative mortality associated with incident diseases was higher among patients treated with chemotherapy (MRR = 10, 95% CI: 8.7, 12) and radiotherapy (MRR = 9.8, 95% CI: 8.8, 11) than among patients who received surgery (MRR = 7.0, 95% CI: 6.7, 7.4) or hormonal therapy (MRR = 6.3, 95% CI: 5.8, 6.9)., Conclusion: There were no marked differences in mortality of diseases among breast cancer survivors and women from the general population. Among breast cancer patients, new diseases were more often fatal in patients treated with chemotherapy and radiotherapy. Five-year breast cancer survivors have similar risk of dying from new chronic medical conditions as women from the general population without breast cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Age is an important risk factor for breast cancer, but previous data has been contradictory on whether patient age at diagnosis is also related to breast cancer survival. The present study evaluates age at diagnosis as a prognostic factor for breast cancer on a large cohort of patients at a single institution., Methods: All 4,453 women diagnosed with breast cancer in Malmö University Hospital, Sweden between 1961 and 1991 were followed up on for 10 years with regards to breast cancer-specific mortality (BCSM) in different age groups. Corresponding relative risks (RR), with 95% confidence intervals, were obtained using Cox's proportional hazards analysis. All analyses were adjusted for potential confounders and stratified for axillary lymph node involvement (ALNI) and diagnostic period., Results: As compared to women aged 40 to 49 years, those who were aged under 40 (RR: 1.40; 95% CI: 1.04 to 1.88) and 80 or more years (RR: 1.80; 95% CI: 1.45 to 2.25) had a statistically significant higher 10-year mortality rate. When adjusted for potential confounders, including stage at diagnosis, the associations only remained statistically significant for women aged 80 years or more. In the analyses stratified on ALNI, ALNI-negative women under 40 years had a statistically significant higher five-year mortality rate (RR: 2.65; 95% CI: 1.23 to 5.70). In the analyses stratified on diagnostic period, the positive association between women aged under 40 or aged 80 or more years and high BCSM rate remained, with statistically significant results for women aged 80 years or more in all periods., Conclusions: Women under 40 years of age had a poor prognosis, and this association was strongest among young women with axillary lymph node negative breast cancer. An age of 80 years or more was a prognostic factor for poor survival, independent of stage at diagnosis and diagnostic period.

Objectives: To assess the interaction between comorbidity and breast cancer (BC) on the rate of venous thromboembolism (VTE) beyond what can be explained by the independent effects of BC and comorbidity., Design: Population-based matched cohort study., Setting: Denmark., Participants: Danish patients with BC (n=62 376) diagnosed in 1995-2010 and a comparison cohort of women without BC (n=304 803) from the general population were matched to the patients with BC on year of birth in 5-year intervals and on the specific diseases included in the Charlson Comorbidity Index (CCI) and atrial fibrillation and obesity., Measures: The rate ratios of VTE per 1000 person-years (PY) were computed by comorbidity levels using the CCI, and interaction contrasts (IC) were calculated as a measure of the excess or deficit VTE rate not explained by the independent effects of BC and comorbidity., Results: Among patients with BC with a CCI score of 1, the 0-1 year VTE rate was 12/1000 PY, and interaction accounted for 10% of the rate (IC=3.2, 95% CI 0.5 to 5.9). Among patients with BC with CCI ≥4, the VTE rate was 17, and interaction accounted for 8% of the rate (IC=1.2, 95% CI -1.8 to 4.2). There was no interaction during 2-5 years of follow-up., Conclusions: There was only little interaction between BC and the CCI score on the rate of VTE., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: During the last decades the diagnosis, treatment, and prognosis of breast cancer have changed and improved in Denmark. The first mammography screening programme started in 1991. However, for many years only about 20% of Danish women aged 50-69 were offered screening. The national roll-out of screening took place in 2008-2010., Material and Methods: Based on published Danish data, this overview describes the status of diagnosis and treatment, and the screening programme. For further evaluating the potential overdiagnosis and overtreatment, additional Danish Breast Cancer Cooperative Group (DBCG) data are included., Results and Conclusion: Using incidence-based mortality method, reduction in breast cancer mortality was estimated to be 25% in the target group of women after 10 years of screening in Copenhagen; an outcome comparable to that of randomised controlled trials. A recent Danish study has indicated overdiagnosis to be around 4%. Others have estimated overdiagnosis to be 33%. National DBCG data showed that the rude breast cancer incidence increased during the period 1990-2011 from 126 to 206 per 100 000. The incidence was almost constant for women younger than 50 years. In regions not offering screening, the incidence increased with 3% per year for women aged 50-69 years with similar trends for small and large tumours. After introduction of screening the increase in the age group 50-69 years was confined to small tumours ≤ 20 mm, and most pronounced for node negative patients. From the 1990s, the use of breast conserving surgery has increased from around 25% to 69% in 2010. Screening has not increased the number of mastectomies. Breast cancer treatment in Denmark is evidence based and in agreement with international recommendations. After the introduction of mammography screening the absolute number of patients with a more advanced stage at diagnosis and the absolute number of patients undergoing mastectomy have decreased.

Background: Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses., Methods: We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non-metastatic breast cancer from 1990-2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95% confidence intervals (95% CI) of BCR. We used random-effects meta-analytic models to evaluate the association of SOD2 polymorphisms and BCR., Results: The frequency of the SOD2-Ala allele was 70% in cases versus 71% in controls; 40% versus 44% were heterozygotes, and 30% versus 25% were homozygotes, respectively. Heterozygote and homozygote carriers of the Ala allele had no increased rate of BCR (OR = 1.1, 95%CI = 0.65, 2.0, and OR = 0.87, 95%CI = 0.47, 1.6, respectively). Five studies informed the meta-analytic models; summary estimates associating BCR for homozygote, or any inheritance of the variant Ala allele were 1.18 (95%CI = 0.74, 1.88), and 1.18, (95%CI = 0.91, 1.54), respectively., Conclusion: Our findings do not suggest that MnSOD enzymatic activity, as measured by SOD2 genotype, affects rates of BCR among patients treated with Cyclo.

Background: Survival of breast cancer patients with comorbidity, compared to those without comorbidity, has been well characterized. The interaction between comorbid diseases and breast cancer, however, has not been well-studied., Methods: From Danish nationwide medical registries, we identified all breast cancer patients between 45 and 85 years of age diagnosed from 1994 to 2008. Women without breast cancer were matched to the breast cancer patients on specific comorbid diseases included in the Charlson comorbidity Index (CCI). Interaction contrasts were calculated as a measure of synergistic effect on mortality between comorbidity and breast cancer., Results: The study included 47,904 breast cancer patients and 237,938 matched comparison women. In the first year, the strongest interaction between comorbidity and breast cancer was observed in breast cancer patients with a CCI score of ≥4, which accounted for 29 deaths per 1000 person-years. Among individual comorbidities, dementia interacted strongly with breast cancer and accounted for 148 deaths per 1000 person-years within one year of follow-up. There was little interaction between comorbidity and breast cancer during one to five years of follow-up., Conclusions: There was substantial interaction between comorbid diseases and breast cancer, affecting mortality. Successful treatment of the comorbid diseases or the breast cancer can delay mortality caused by this interaction in breast cancer patients.

Purpose: To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort., Patients and Methods: We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year., Results: Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3)., Conclusion: Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk.

Aim: To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation., Methods: We conducted a population-based study in Denmark. Patients were categorized according to age group, surgery type, and glucocorticoid use before surgery: never, current (0-90 days), and former (>90 days). We calculated the risk of re-operation due to post-surgical bleeding within 14 days after surgery, risk differences, and risk ratios of re-operation associated with age group, surgery type, and glucocorticoid use., Results: 19,919 women were studied; 508 were re-operated. 3573 of the 19,919 women ever used glucocorticoids. Older age and mastectomy increased the risk of post-surgical bleeding compared with breast conserving surgery and younger age among both ever and never users of glucocorticoids. The crude risk of re-operation was 2.5% among never users of glucocorticoids, 2.6% among ever users and 4.0% among current users. Women aged ≥80 who were ever users of glucocorticoids and who had a mastectomy had 8.1% risk of re-operation due to post-surgical bleeding, whereas women <80 years old who never used glucocorticoids and who had breast conserving surgery had a 1.7% risk of re-operation., Conclusions: Older age, mastectomy, and - in some women - glucocorticoid use add an extra risk of re-operation due to bleeding. Clinicians and their patients can use this information to evaluate the patient-specific risk of this complication., (Copyright © 2012. Published by Elsevier Ltd.)

Background: Estrogen receptor (ER) expression predicts tamoxifen response, which halves the risk of breast cancer recurrence. We examined clinical factors associated with concordance between ER expression at diagnosis and centralized re-assay, and the association of concordance with breast cancer recurrence., Material and Methods: We used immunohistochemistry to assess ER expression on archived fixed, paraffin-embedded breast carcinoma tissue excised from women aged 35-69 years, diagnosed 1985-2001 in Jutland, Denmark. We calculated the percentage agreement, positive predictive value (PPV) and negative predictive value (NPV) of ER status at diagnosis and re-assay. We used logistic regression to investigate factors associated with concordance, and its association with recurrence (odds ratios (OR) and associated 95% confidence intervals (95%CI))., Results: ER was re-assayed in 91% of patients (n = 1530). Concordance was better in ER + than ER- tumors (PPV = 94% vs. NPV = 75%). Factors associated with concordance included menopausal status, tumor size, surgical procedure, diagnostic period, lymph node status and time to recurrence. ER + women at diagnosis who re-assayed ER + were less likely to have recurrent disease (OR = 0.49, 95% CI = 0.28, 0.86) than those who re-assayed ER-. In originally ER- women, concordance was not associated with recurrence (OR = 0.97, 95% CI = 0.66, 1.42)., Conclusions: Several clinical factors were associated with ER assay concordance. Some women were ineffectively treated with tamoxifen, or required but did not receive tamoxifen. We observed almost exactly the protective effect of endocrine therapy among tamoxifen-treated ER + women whose tumors expressed the ER on re-assay, compared with those ER- on re-assay. Diagnostic pathology results for ER + tumors appear a valid and useful resource for research studies. However, those for ER- tumors have lower validity. Study-specific considerations regarding the aims, diagnostic period, and consequences of including ER- patients with truly ER + disease ought to be examined when using diagnostic pathology results for ER- tumors in research studies.

Background: The purpose of this study was to investigate the completeness of TNM (Tumor, Node, Metastasis) staging for breast cancer in the Danish Cancer Registry., Methods: We identified 26,488 patients with a first diagnosis of breast cancer between 2004 and 2009 from the Danish Cancer Registry. We obtained information on comorbidity through the Danish National Patient Registry. We estimated the completeness of TNM registration in the Danish Cancer Registry and stratified the analysis by gender, age, year of cancer diagnosis, and comorbidity. We designed an algorithm categorizing breast cancer into localized, regional, distant, or unknown stage based on TNM codes., Results: The overall completeness of TNM registration was 85.4%. The completeness varied little by gender and study year, but decreased from 91.3% in patients aged 0-39 years to 57.0% in patients aged 80 years or more, and from 87.9% among patients with a low level of comorbidity to 69.7% among patients with a high level of comorbidity., Conclusion: The completeness of the TNM registration varied substantially by age and level of comorbidity. Thus, depending on the outcome under study, stage-specific analyses may yield biased results. The completeness of TNM should be considered in study designs using TNM information.

Introduction: Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth., Methods: Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods., Results: The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment., Conclusions: There was no substantial association between morbidity measured with the CCI and breast cancer risk.

Background: Accumulating evidence suggests that statins affect diseases other than cardiovascular disease, including cancer, and that these effects may depend on the lipid solubility of specific statins. Though many studies have reported an association between statin use and breast cancer incidence, the relationship between statin use and breast cancer recurrence has not been well studied., Methods: We conducted a nationwide, population-based prospective cohort study of all female residents in Denmark diagnosed with stage I-III invasive breast carcinoma who were reported to the Danish Breast Cancer Cooperative Group registry between 1996 and 2003 (n = 18,769). Women were followed for a median of 6.8 years after diagnosis. Prescriptions for lipophilic and hydrophilic statins were ascertained from the national electronic pharmacy database. Associations between statin prescriptions and breast cancer recurrence were estimated with generalized linear models and Cox proportional hazards regression with adjustment for age and menopausal status at diagnosis; histological grade; estrogen receptor status; receipt of adjuvant therapy; type of primary surgery received; pre-diagnosis hormone replacement therapy; and co-prescriptions of aspirin, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or anticoagulants. All statistical tests were two-sided., Results: Most prescriptions for lipophilic statins in the study population were for simvastatin. Exclusive simvastatin users experienced approximately 10 fewer breast cancer recurrences per 100 women after 10 years of follow-up (adjusted 10-year risk difference = -0.10, 95% confidence interval = -0.11 to -0.08), compared with women who were not prescribed a statin. Exclusive hydrophilic statin users had approximately the same risk of breast cancer recurrence as women not prescribed a statin over follow-up (adjusted 10-year risk difference = 0.05, 95% confidence interval = -0.01 to 0.11)., Conclusions: Simvastatin, a highly lipophilic statin, was associated with a reduced risk of breast cancer recurrence among Danish women diagnosed with stage I-III breast carcinoma, whereas no association between hydrophilic statin use and breast cancer recurrence was observed.

Background: Tamoxifen is oxidized by cytochrome-P450 enzymes (e.g., CYP2D6) to two active metabolites, which are eliminated via glucuronidation by UDP-glucuronosyl transferases (UGT). We measured the association between functional polymorphisms in key UGTs (UGT2B15*2, UGT2B7*2, and UGT1A8*3) and the recurrence rate among breast cancer survivors., Methods: We used the Danish Breast Cancer Cooperative Group registry to identify 541 cases of recurrent breast cancer among women with estrogen receptor-positive tumors treated with tamoxifen for at least 1 year (ER(+)/TAM(+)), and 300 cases of recurrent breast cancer among women with estrogen receptor-negative tumors who were not treated with tamoxifen (ER(-)/TAM(-)). We matched one control to each case on ER status, menopausal status, stage, calendar period, and county. UGT polymorphisms were genotyped from archived primary tumors. We estimated the recurrence OR for the UGT polymorphisms by using logistic regression models, with and without stratification on CYP2D6*4 genotype., Results: No UGT polymorphism was associated with breast cancer recurrence in either the ER(+)/TAM(+) or ER(-)/TAM(-) groups [in the ER(+)/TAM(+) group, compared with two normal alleles: adjusted OR for two UGT2B15*2 variant alleles = 1.0 (95% CI, 0.70-1.5); adjusted OR for two UGT2B7*2 variant alleles = 0.96 (95% CI, 0.65-1.4); adjusted OR for one or two UGT1A8*3 variant alleles = 0.95 (0.49-1.9)]. Associations were similar within strata of CYP2D6*4 genotype., Conclusions: Functional polymorphisms in key tamoxifen-metabolizing enzymes were not associated with breast cancer recurrence risk., Impact: Our results do not support the genotyping of key metabolic enzyme polymorphisms to predict response to tamoxifen therapy.

Mammography screening is offered healthy women, and a high standard on professional and organizational level is mandatory not only in the screening programme but even in the diagnostic work-up and treatment. The main goal is to achieve a substantial reduction in disease specific mortality, but it is not possible to evaluate the effect on mortality until several years later, and continuously monitoring of the quality of all aspects of a screening programme is necessary. Based on other European guidelines, 11 quality indicators have been defined, and guidelines concerning organizational requirements for a Danish screening programme as well as recommendations for the radiographic and radiological work have been drawn up.

Background: Cytochrome P450 2D6 (CYP2D6) inhibition reduces the concentration of 4-hydroxylated tamoxifen metabolites, but the clinical relevance remains uncertain., Methods: We conducted a large case-control study nested in the population of 11 251 women aged 35-69 years at diagnosis of stage I-III breast cancer between 1985 and 2001 on Denmark's Jutland Peninsula and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent or contralateral breast cancers among women with estrogen receptor-positive (ER+) disease treated with tamoxifen for at least 1 year and 300 cancers in women with ER-negative (ER-) disease never treated with tamoxifen. We matched one control subject per case patient on ER status, menopausal status, stage, calendar time, and county, genotyped the CYP2D6*4 allele to assess genetic inhibition, and ascertained prescription history to assess drug-drug inhibition. We estimated the odds ratio (OR), associating CYP2D6 inhibition with breast cancer recurrence and adjusted for potential confounding with logistic regression. To address bias from incomplete information on CYP2D6 function, we used Monte Carlo simulation to complete a record-level probabilistic bias analysis. All statistical tests were two-sided., Results: The frequency of the CYP2D6*4 minor allele was 24% in case patients with ER+ tumors, 23% in case patients with ER- tumors, and 22% each in control subjects with ER+ and ER- tumors. In women with ER+ tumors, the associations of one functional allele with recurrence (OR = 0.99; 95% confidence interval = 0.76 to 1.3) and no functional allele with recurrence (OR = 1.4; 95% confidence interval = 0.84 to 2.3) were near null, as were those for women with ER- tumors. The near-null associations persisted when evaluated by intake of medications, by combining genotype with medication history, in the probabilistic bias analysis, or by restricting the analysis to women with ER expression confirmed by re-assay., Conclusion: The association between CYP2D6 inhibition and recurrence in tamoxifen-treated patients is likely null or small.

Background: Up to one-quarter of breast cancer patients suffer clinically significant depression in the year after diagnosis, which may respond to intervention. About half may be prescribed a psychotropic medication, such as a selective serotonin reuptake inhibitor (SSRI), while completing breast cancer therapy. Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms. Therefore, concurrent use of SSRIs may reduce tamoxifen's effectiveness at preventing breast cancer recurrence. The SSRI citalopram has limited potency to inhibit CYP2D6 activity, so has been recommended for breast cancer patients taking tamoxifen. This study provides epidemiologic evidence to support this recommendation., Material and Methods: We conducted a case-control study of breast cancer recurrence nested in the population of female residents of Denmark who were diagnosed with non-metastatic estrogen-receptor positive breast cancers between 1994 and 2001 and who took tamoxifen for at least one year. We ascertained complete prescription histories by linking cases' and controls' civil registration numbers to the Danish national prescription registry. We estimated the association between SSRI use while taking tamoxifen and risk of recurrent breast cancer., Results: About the same proportion of recurrent cases (37 of 366) and matched controls (35 of 366) received at least one prescription for citalopram or its s-stereoisomer while taking tamoxifen (adjusted odds ratio = 1.1, 95% confidence interval = 0.7, 1.7). Breast cancer patients taking other SSRIs were also at no increased risk of recurrence (adjusted odds ratio = 0.9, 95% confidence interval = 0.5, 1.8)., Discussion: Breast cancer patients with indications for an SSRI may be prescribed citalopram - and possibly other SSRI - without adversely affecting the outcome of adjuvant therapy with tamoxifen.

Aims: Mammographic screening reduces mortality in breast cancer. It is not known if this reduction is more pronounced in certain groups. Obesity has been associated with worse survival following breast cancer diagnosis. This study investigates BMI in relation to breast cancer mortality, and if this association is affected by invitation to mammographic screening., Methods: In 1976, a randomised mammographic screening trial, inviting 50% of all women aged 45-69 years (n=42 283), was set up in Malmö, Sweden. BMI in relation to breast cancer mortality was examined separately in women invited or not invited to screening in the trial. The analyses also included a historical control-group diagnosed before the screening trial. The study included 2974 women diagnosed in 1961-1991. Relative risks (RR) with a 95% confidence interval was obtained from a Cox proportional hazard analysis and in the analysis of all women, follow-up was limited to 10 years., Results: Obese women (BMI> or =30) not invited to mammographic screening had a higher adjusted RR of dying of breast cancer as compared to normal weight women (2.08:1.13-3.81) in the 10-year follow-up. In women invited to screening there was no association between BMI and breast cancer mortality. In the historical control group, mortality was increased in overweight women (BMI: 25-30), RR=1.27:0.99-1.62, and obese women, RR=1.32:0.94-1.84, but these associations totally disappeared in the multivariate analysis, following adjustment for tumour size and stage., Conclusions: Overweight and obese women may be a group that profit from mammographic screening to more than normal weight women.

Objectives: Overweight is associated with advanced stage at diagnosis in breast cancer patients. This could be explained by specific tumour characteristics or tumour promoting factors in the obese, but a diagnostic delay could also be of importance. Mammographic screening has caused a change towards diagnosis of less advanced tumours. This study investigates invitation to mammographic screening and the association between overweight and tumour size/axillary lymph node involvement at breast cancer diagnosis in postmenopausal women., Methods: In 1976 a randomized mammographic screening trial, inviting 50% of all women aged 45-69 was set up in Malmö, Sweden. The present analysis examined overweight (body mass index >or=25) as a determinant for large tumours (>20mm) and axillary lymph node involvement in postmenopausal women. These associations were studied separately in patients diagnosed prior to the mammographic screening trial, in invited women and in non-invited subjects (controls). In all, 2478 postmenopausal women were diagnosed with invasive breast cancer in these groups between 1961 and 1991. Logistic regression analysis allowed adjustment for other potential determinants of tumours size and axillary lymph node involvement., Results: In women diagnosed before the onset of the screening trial and in women not invited to mammography in the trial (controls), overweight was positively associated with large tumour size and axillary node involvement. There was no statistically significant association between overweight and these factors in women invited to mammographic screening., Conclusion: Invitation to mammographic screening may be particularly important for overweight postmenopausal women in order to detect breast tumours early.

Aim: The present study examines the association between parity and survival following breast cancer diagnosis., Methods: Medical records of 4453 women diagnosed with breast cancer in Malmö, Sweden, between 1961 and 1991 were analysed. All women were followed until 31 December 2003, using the Swedish Cause-of-Death Registry. Breast cancer specific mortality rate was calculated in different levels of parity. Corresponding relative risks, with 95% confidence intervals (CI), were obtained using Cox's proportional hazards analysis. All analyses were adjusted for potential prognostic factors and stratified for age, menopausal status and diagnostic period., Results: As compared to women with one child, nulliparity (RR 1.27: 95% CI 1.09-1.47), and high parity (four or more children) (1.49: 1.20-1.85) were positively associated with a high mortality from breast cancer. When adjusted for potential confounders, the association was only statistically significant for high parity (1.33: 1.07-1.66). In the analyses stratified on age and menopausal status, there was a similar positive association between high parity and breast cancer death in all strata, although only statistically significant among women older than 45 years of age or postmenopausal. Nulliparity was associated with breast cancer death in women that were younger than 45 years of age (1.28: 0.79-2.09) or premenopausal (1.30: 0.95-1.80), but these associations did not reach statistical significance. There was no association between nulliparity and breast cancer death in women older than 45 years of age or postmenopausal. All associations were similar in analyses stratified for diagnostic period., Conclusion: Women with four or more children have a poor breast cancer survival as compared to women with one child.

Tamoxifen remains an important adjuvant therapy to reduce the rate of breast cancer recurrence among patients with oestrogen-receptor-positive tumours. Cytochrome P-450 2D6 metabolizes tamoxifen to metabolites that more readily bind the oestrogen receptor. This enzyme also metabolizes selective serotonin reuptake inhibitors (SSRI), so these widely used drugs - when taken concurrently - may reduce tamoxifen's prevention of breast cancer recurrence. We studied citalopram use in 184 cases of breast cancer recurrence and 184 matched controls without recurrence after equivalent follow-up. Cases and controls were nested in a population of female residents of Northern Denmark with stages I-III oestrogen-receptor-positive breast cancer 1985-2001 and who took tamoxifen for 1, 2, or most often for 5 years. We ascertained prescription histories by linking participants' central personal registry numbers to prescription databases from the National Health Service. Seventeen cases (9%) and 21 controls (11%) received at least one prescription for the SSRI citalopram while taking tamoxifen (adjusted conditional odds ratio=0.85, 95% confidence interval=0.42, 1.7). We also observed no reduction of tamoxifen effectiveness among regular citalopram users (>or=30% overlap with tamoxifen use). These results suggest that concurrent use of citalopram does not reduce tamoxifen's prevention of breast cancer recurrence.

Using hospital discharge data from the counties in Northern Denmark and the Danish Cancer Registry, we examined the trend in the prevalence of breast-conserving surgery (BCS) to treat primary breast cancer from 1982 through 2002, with an emphasis on publications that may have influenced surgical practice in Denmark. Overall, the prevalence of BCS increased from less than 1% of breast cancer operations in 1982 to approximately 25% by 2002. The rise in prevalence was most pronounced for the treatment of young women and women with early-stage breast cancer. Of three pivotal clinical trials, the most significant trigger of the upward trend appeared to be a study conducted by the Danish Breast Cancer Cooperative Group, published in 1988. After 1988, there was a steep rise in the prevalence of BCS. By 2002, BCS prevalence appeared to reach a threshold at 25% of breast cancer operations, seemingly defined by the proportion of new breast cancer cases who are good candidates for BCS.

Background: The validation series of sentinel lymph node biopsy (SLNB) in the treatment of breast cancer have shown that 10-20% more lymph node metastases are detected. However, their impact has never been studied in populations where the method has been fully implemented. In a population-based setting, the objective of the current study was to estimate the increased risk of metastases after introduction of the sentinel lymph node biopsy technique., Methods: We identified all new breast cancer patients in three different counties in two time periods (1996-1997 and 2002-2003). The study cohort was comprised of 2 932 patients. The main outcome was the frequency of patients with metastases. The frequencies of patients with metastases were compared as well as adjusted (using a multivariate logistic regression) and unadjusted odds-ratio for detecting lymph node metastases., Results: In counties where sentinel lymph node biopsy was implemented, the frequency of patients with lymph node metastases increased significantly 7.3% (95% CI: 1.0-13.7%) and 13.3% (95% CI: 7.3-19.3%), respectively. In the county without sentinel lymph node biopsy, an insignificant increase of 6.9% (-0.1-13.9%) in the frequency of patients with metastases was seen. The adjusted odds- ratio for detecting lymph node metastases was 1.41 (1.07-1.87) and 1.70 (1.30-2.23) in the counties with SLNB., Conclusion: The frequency of patients with metastases increased significantly in counties where sentinel lymph node biopsy was implemented.

Prior to the initiation of a nationwide study of the sentinel node staging technique the Danish Breast Cancer Cooperative Group (DBCG) defined a set of minimum requirements to be met by surgical departments before they could include patients in the study. The requirements specified a minimum patient load in the individual surgical unit, a minimum surgical training in the sentinel node biopsy technique and a minimum quality outcome in a validating learning series of SNLB procedures. A working group assisted departments in meeting these terms and later audited and certified departments before they could include patients into the study. As a result of this strategy the sentinel lymph node staging was fully implemented in all Danish surgical breast cancer centres within three years and all sentinel node biopsies in the period were recorded in the DBCG data centre. Furthermore, the strategy accelerated the ongoing process of centralizing breast surgery in specialized departments.

Comorbid diseases can affect breast cancer prognosis. We conducted a population-based study of Danish women diagnosed with a first primary breast cancer from 1995 to 2005 (n=9300), using hospital discharge registry data to quantify comorbidities by Charlson score. We examined the influence of comorbidities on survival, and quantified their impact on relative mortality rates. The prevalence of patients with a Charlson score='0' fell from 86 to 81%, with an increase in those with Charlson score='1-2' from 13 to 16%, and score='3+' from 1 to 2%. One- and five-year survival for patients with Charlson score='0' and '1-2' was better for those diagnosed in 1998-2000 than in 1995-1997. Overall, patients diagnosed in 2001-2004 (mortality ratio (MR)=0.80, 95% CI=0.68-0.95) and 1998-2000 (MR=0.92, 95% CI=0.78-1.09) had lower 1-year age-adjusted mortality compared to those diagnosed in 1995-1997 (reference period). Patients with Charlson scores '1-2' and '3+' had higher age-adjusted 1-year mortality than those with a Charlson score='0' in each time period (2001-2004: MR('1-2')=1.76, 95% CI=1.35-2.30, and MR('3+')=3.78, 95% CI=2.51-5.68; and 1998-2000: MR('1-2')=1.60, 95% CI=1.36-1.88 and MR('3+')=2.34, 95% CI=1.65-3.33). Similar findings were observed for 5-year age-adjusted mortality. Additional analyses, adjusted for stage, indicated that confounding by stage could not explain these findings. Despite continued improvements in breast cancer survival, we found a trend of poorer survival among breast cancer patients with severe comorbidities even after adjusting for age and stage. Such poorer survival is an important public health concern and can be expected to worsen as the population ages.

Objective: To investigate the association between parity and axillary lymph node involvement (ALNI) at breast cancer diagnosis., Methods: One surgeon has reviewed all breast cancer cases in Malmo, Sweden, diagnosed 1961-1991. This study includes the 3,472 women who had a first-time diagnosis of unilateral invasive breast cancer, and who had undergone axillary dissection. Information was collected regarding date of birth, date of diagnosis, age at diagnosis, menopausal status, tumour size, histological type, tumour location, type of surgery, stage (ALNI), and parity. Parity was investigated in relation to ALNI using logistic regression analysis, adjusted for potential confounders, yielding odds ratios (OR) with 95% confidence intervals (CI). The analyses were repeated in different strata with regard to birth-years cohort, age at diagnosis, and period of diagnosis., Results: High parity was associated with ALNI, the adjusted OR for ALNI among women with 4 or more children was 1.56 (1.13-2.15). This association was stronger in comparatively old women (> or = 67.45 years), OR 1.78 (1.10-2.88). Considering parity a continuous variable, the OR for ALNI among all women was 1.06 (1.01-1.12)., Conclusions: We conclude that women with 4 or more children had an increased risk of ALNI at breast cancer diagnosis., (Copyright 2005 S. Karger AG, Basel.)