The impact of prior psychiatric medical treatment on return to work after a diagnosis of breast cancer: A registry based study.

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.

Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue.

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.

The long-term financial consequences of breast cancer: a Danish registry-based cohort study.

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.

Sentinel Lymph Node Dissection in Locally Recurrent Breast Cancer.

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.

Age at diagnosis in relation to survival following breast cancer: a cohort study.

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.

Position paper: breast cancer screening, diagnosis, and treatment in Denmark.

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.

Factors associated with concordant estrogen receptor expression at diagnosis and centralized re-assay in a Danish population-based breast cancer study.

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.

Mammography screening in Denmark.

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.

Breast cancer recurrence risk related to concurrent use of SSRI antidepressants and tamoxifen.

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.

Organized nation-wide implementation of sentinel lymph node biopsy in Denmark.

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.

Can registry data be used as a proxy for perceived stress? A cross-sectional study.

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.

Relative mortality rates from incident chronic diseases among breast cancer survivors--a 14 year follow-up of five-year survivors diagnosed in Denmark between 1994 and 2007.

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.

Impact of comorbidity on risk of venous thromboembolism in patients with breast cancer: a Danish population-based cohort study.

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.

Manganese superoxide dismutase and breast cancer recurrence: a Danish clinical registry-based case-control study, and a meta-analysis.

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.

Comorbid diseases interact with breast cancer to affect mortality in the first year after diagnosis--a Danish nationwide matched cohort study.

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.

Use of ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and risk of breast cancer recurrence: a Danish nationwide prospective cohort study.

PURPOSE: To estimate associations between use of ß-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. ß-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 ß-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 ß-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 ß-blockers attenuate breast cancer recurrence risk.

Completeness of breast cancer staging in the Danish Cancer Registry, 2004-2009.

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.

Hospital recorded morbidity and breast cancer incidence: a nationwide population-based case-control study.

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.