Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups.

Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14-2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09-2.66]; HRadj:1.75 [95% CI = 1.08-2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78-3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62-3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95-6.87]; HRadj:1.92 [95% CI = 1.06-3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64-3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.

Hospital-diagnosed overweight and obesity related to cancer risk: a 40-year Danish cohort study.

BACKGROUND: Obesity is associated with metabolic abnormalities that predispose patients to increased cancer risk. Contemporary data on the long-term risk of specific cancers are sparse among patients with hospital-diagnosed overweight and obesity. OBJECTIVES: To examine the overall cancer incidence and specific site-related cancer incidences among patients with overweight and obesity, compared to the general Danish population. METHODS: For this 40-year (1977-2016), nationwide, Danish cohort study, we reviewed medical databases to identify individuals with hospital-based overweight and obesity diagnoses. We computed age- and gender-standardized incidence ratios (SIRs) for subsequent cancer compared to the general population. RESULTS: We observed 20 706 cancers among 313 321 patients diagnosed with overweight and obesity (median age 43 years; median follow-up 6.7 years, range 1-40 years) compared to the 18 480 cancers expected; thus, the SIR was 1.12 [95% confidence interval (95% CI): 1.11-1.14]. The SIR associated with overweight and obesity was increased with concomitant comorbidities, like type 2 diabetes (SIR: 1.18; 95% CI: 1.13-1.23) and alcoholism-related diseases (SIR: 1.62; 95% CI: 1.45-1.82). The SIR was 1.31 (95% CI: 1.28-1.34) for cancers previously identified as obesity-related, including pancreatic (SIR: 1.38; 95% CI; 1.27-1.49) and postmenopausal breast cancer (SIR: 1.14; 95% CI: 1.09-1.19). Obesity/overweight status also elevated the SIRs for haematological (SIR: 1.24; 95% CI: 1.18-1.29) and neurological cancers (SIR: 1.19; 95% CI: 1.11-1.27]. In contrast, SIRs were 1.01 (95% CI: 0.97-1.05) for immune-related cancers, 0.88 (95% CI: 0.82-0.95) for malignant melanoma, and 0.88 (95% CI: 0.85-0.92) for hormone-related cancers, other than postmenopausal breast cancer. CONCLUSION: In this large cohort study, overweight and obesity was associated with increased risk of several common cancers.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Herpes zoster as a marker of occult cancer: A systematic review and meta-analysis.

OBJECTIVES: Researchers have advocated for an increased awareness of occult cancer among herpes zoster patients, but there are no systematic reviews to support these claims. We therefore conducted a systematic review and meta-analysis of evidence on zoster and risk of occult cancer. METHODS: Through February 18, 2016, we searched PubMed, EMBASE and references of relevant papers for studies on zoster and risk of any cancer. One author screened retrieved papers by title and abstract; included papers were reviewed by two authors for eligibility, data extraction, and potential biases. Despite statistical heterogeneity, associations were consistently in the same direction and we therefore computed pooled relative risks using random-effects models. RESULTS: We identified 46 eligible studies, 10 of which considered all cancer types combined. The pooled relative risk for any cancer was 1.42 (95% confidence interval: 1.18, 1.71) overall and 1.83 (95% confidence interval: 1.17, 2.87) at one year after zoster. Considering cancer subtypes, the highest estimates were generally reported for occult hematological cancer. The absolute risk of any cancer at one year after presentation with zoster was 0.7-1.8%. CONCLUSION: This study supports an association between zoster and occult cancer, but the low absolute risk of cancer limits the clinical implications.

Body mass index, risk of allogeneic red blood cell transfusion, and mortality in elderly patients undergoing hip fracture surgery.

UNLABELLED: Despite improvements in preoperative and postoperative treatment, hip fracture surgery may lead to blood transfusion. Little is known about the impact of body mass index on transfusion risk and subsequent mortality. Opposite overweight and obese patients, underweight patients had increased risk of transfusion and death within 1 year of surgery. INTRODUCTION: Despite improvements in preoperative and postoperative treatment of hip fracture patients, hip fracture surgery may lead to blood loss. We examined the risk of red blood cell transfusion (as an indirect measure of blood loss) and subsequent mortality by body mass index level in patients aged 65 and over undergoing hip fracture surgery. METHODS: This is a population-based cohort study using medical databases. We included all patients who underwent surgery for hip fracture during 2005-2013. We calculated the cumulative risk of red blood cell transfusion within 7 days of surgery treating death as a competing risk and, among transfused patients, short- (8-30 days postsurgery) and long-term mortality (31-365 days postsurgery). RESULTS: Among 56,420 patients, 47.7 % received at least one red blood cell transfusion within 7 days of surgery. In patients with normal weight, the risk was 48.8 % compared with 57.0 % in underweight patients (adjusted RR = 1.11; CI 1.08-1.15), 42.1 % in overweight patients (adjusted RR = 0.89; CI 0.86-0.91), and 42.2 % in obese patients (adjusted RR = 0.87; CI 0.84-0.91). Among transfused patients, adjusted HRs for short-term mortality were 1.52 (CI 1.34-1.71), 0.70 (CI 0.61-0.80), and 0.58 (CI 0.43-0.77) for underweight, overweight, and obese patients, respectively, compared with normal-weight patients. The corresponding adjusted HRs for long-term mortality were 1.45 (CI 1.33-1.57), 0.80 (CI 0.74-0.86), and 0.58 (CI 0.50-0.69). Similar association between BMI and mortality was observed also among non-transfused patients. CONCLUSIONS: Underweight patients had a higher risk of red blood cell transfusion and death in the first year of surgery than normal-weight patients, even when controlling for age and comorbidity. Opposite findings were seen for overweight and obese patients.

Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study.

BACKGROUND: Treatment with synthetic glucocorticoids (GCs) depresses the immune response and may therefore modify cancer outcomes. We investigated the association between GC use and breast cancer recurrence. MATERIALS AND METHODS: We conducted a population-based cohort study to examine the risk of breast cancer recurrence associated with GC use among incident stage I-III female breast cancer patients aged >18 years diagnosed 1996-2003 in Denmark. Data on patients, clinical and treatment factors, recurrence, and comorbidities as well as data on GC prescriptions and potential confounders were obtained from Danish population-based medical registries. GCs were categorized according to administrative route: systemic, inhaled, or intestinal. Women were followed for up to 10 years or until 31 December 2008. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) to evaluate the association between GC use and recurrence. Time-varying drug exposures were lagged by 1 year. RESULTS: We included 18 251 breast cancer patients. Median recurrence follow-up was 6.9 years; 3408 women developed recurrence during follow-up. Four thousand six hundred two women filled at least one GC prescription after diagnosis. In unadjusted models, no association was observed among users of systemic, inhaled, and intestinal GCs (HRsystemic = 1.1, 95% CI 0.9-1.3; HRinhaled = 0.9, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.9-1.2) versus nonusers. In adjusted models, the results were also near null (HRsystemic = 1.1, 95% CI 0.9-1.2; HRinhaled = 0.8, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.8-1.2). CONCLUSION: We found no evidence of an effect of GC use on breast cancer recurrence.

Mortality and incidence of new primary cancers in men with prostate cancer: a Danish population-based cohort study.

BACKGROUND: Prostate cancer (PC) survivors may have an increased risk of new primary cancers (NPCs) due to shared risk factors or PC-directed treatments. METHODS: Using Danish registries, we conducted a cohort study of men with (n=30,220) and without PC (n=151,100) (comparators), matched 1:5 on age and PC diagnosis/index date. We computed incidence rates of NPCs per 10,000 person years (PY) and associated 95% confidence intervals (CI), and used Cox proportional hazards regression to compute hazard ratios (HRs) and 95%CI, adjusting for comorbidities. In order to obviate any impact of shorter survival among prostate cancer patients, we censored comparator patients when the matched prostate cancer patient died or was censored. RESULTS: Follow-up spanned 113,487PY and 462,982PY in the PC and comparison cohorts, respectively. 65% of the cohorts were aged >70 years at diagnosis. Among PC patients, 51% had distant/unspecified stage, and 63% had surgery as primary treatment. The PC cohort had lower incidence of NPCs than their comparators. The adjusted HR of NPC among men with PC versus the comparators was 0.84 (95%CI=0.80, 0.88). Lowest HRs were among older men, those with distant stage, and were particularly evident for cancers of the brain, liver, pancreas, respiratory, upper gastrointestinal, and urinary systems. CONCLUSIONS: We find no evidence of an increased risk of NPCs among men with PC. The deficit of NPCs among men with PC may be a true effect but is more likely due to lower levels of risk factors (e.g., smoking) in PC patients versus comparators, clinical consideration of cancers at new organs as metastases rather than new primaries, or under-recording/under-reporting of NPCs among PC patients.

Predictors of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study.

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.

Antidepressant use and colorectal cancer risk: a Danish population-based case-control study.

BACKGROUND: Earlier research suggests that use of selective serotonin reuptake inhibitors (SSRIs), but not tricyclic antidepressants (TCAs), reduces the risk of colorectal cancer (CRC). METHODS: We conducted a population-based case-control study to investigate the association between antidepressant use and CRC risk. Cases were diagnosed with a first primary CRC from 1991 through 2008. We selected 10 population controls matched to cases on sex, birth year, and residence from the Danish Civil Registration System using risk-set sampling. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating antidepressant use with colorectal cancer occurrence, controlling for potential confounders. RESULTS: The study included 9,979 cases and 99,790 controls. We found no notable reduction in CRC risk in ever users (≥2 prescriptions) of TCAs (OR=0.94; 95% CI: 0.84, 1.05), SSRIs (OR=0.97; 95% CI: 0.90, 1.05), or other antidepressants (OR=0.95; 95% CI: 0.83, 1.07). Associations for recent and former use of antidepressants were also near null. Intensity of antidepressant use (number of pills divided by total duration of use), regardless of duration, was not associated with CRC risk. CONCLUSIONS: We found no evidence that antidepressant use substantially reduces the risk of colorectal cancer.

Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997-2006.

BACKGROUND: Venous thromboembolism (VTE) frequently complicates cancer. Data on tumour-specific VTE predictors are limited, but may inform strategies to prevent thrombosis. METHODS: We computed incidence rates (IRs) with 95% confidence intervals (CIs) for VTE hospitalisation in a cohort of cancer patients (n=57,591) and in a comparison general-population cohort (n=287,476) in Denmark. The subjects entered the study in 1997-2005, and the follow-up continued through 2006. Using Cox proportional-hazards regression, we estimated relative risks (RRs) for VTE predictors, while adjusting for comorbidity. RESULTS: Throughout the follow-up, VTE IR was higher among the cancer patients (IR=8.0, 95% CI=7.6-8.5) than the general population (IR=4.7, 95% CI=4.3-5.1), particularly in the first year after cancer diagnosis (IR=15.0, 95% CI=13.8-16.2, vs IR=8.6, 95% CI=7.6-9.9). Incidence rates of VTE were highest in patients with pancreas (IR=40.9, 95% CI=29.5-56.7), brain (IR=17.7, 95% CI=11.3-27.8) or liver (IR=20.4, 95% CI=9.2-45.3) tumours, multiple myeloma (IR=22.6, 95% CI=15.4-33.2) and among patients with advanced-stage cancers (IR=27.7, 95% CI=24.0-32.0) or those who received chemotherapy or no/symptomatic treatment. The adjusted RR (aRR) for VTE was highest among patients with pancreas (aRR=16.3, 95% CI=8.1-32.6) or brain cancer (aRR=19.8 95% CI=7.1-55.2), multiple myeloma (aRR=46.1, 95% CI=13.1-162.0) and among patients receiving chemotherapy, either alone (aRR=18.5, 95% CI=11.9-28.7) or in combination treatments (aRR=16.2, 95% CI=12.0-21.7). CONCLUSIONS: Risk of VTE is higher among cancer patients than in the general population. Predictors of VTE include recency of cancer diagnosis, cancer site, stage and the type of cancer-directed treatment.

Is there under-treatment of pancreatic cancer? Evidence from a population-based study in Ireland.

Although clinical trials suggest that chemotherapy can improve survival for both resected and unresected pancreatic cancer patients, the extent to which it is used in routine clinical practice is unclear. We conducted a population-based investigation of treatment patterns and factors influencing treatment receipt and mortality for pancreatic cancer. We included 3173 patients with primary invasive pancreatic cancer, diagnosed in 1994-2003, from the National Cancer Registry (Ireland). Analysis was done by joinpoint regression, logistic regression and Cox proportional hazards. Propensity score methods were used to compare mortality in those who received chemotherapy and in 'matched' patients who did not. Seven percent of patients had a resection and 12% received chemotherapy. The resection rate did not change significantly over time and less than a quarter of patients with localised disease underwent resection. Chemotherapy use increased by 20% per annum, reaching 20% among unresected and 39% among resected patients in 2002-2003. Forty two percent of patients were untreated, and this percentage was unchanged over time. After adjusting for clinical factors, patient characteristics were significantly associated with treatment receipt; older and unmarried patients were less likely to be treated. Among resected patients, risk of death fell by 10% per annum. Chemotherapy receipt was associated with significantly reduced mortality among both surgical (hazard ratio (HR)=0.50, 95% confidence intervals (CIs) 0.27-0.91) and non-surgical patients (HR=0.48, 95% CI 0.38-0.61). Our findings suggest that there may be potential for extended dissemination of chemotherapy, and possibly also for greater utilisation of curative resection, in routine practice which, in turn, has potential to improve survival at the population level.

Inequity in colorectal cancer treatment and outcomes: a population-based study.

Several uncertainties surround optimal management of colorectal cancer. We investigated treatment patterns and factors influencing treatment receipt and mortality in routine clinical practice. We included 15 249 individuals, recorded by the National Cancer Registry (Ireland), with primary invasive colon or rectal tumours, diagnosed during 1994-2002. Logistic regression and Cox proportional hazards were used to determine factors associated with treatment receipt within 1 year of diagnosis and with mortality, respectively. A total of 78% had colorectal resection, 31% chemotherapy, and 13% radiotherapy (4% colon; 28% rectum). Half of stage IV patients underwent resection. Chemotherapy and radiotherapy use increased by at least 10% per annum. There was a notable increase in pre-operative radiotherapy from 2000 onwards. Patient-related factors were significantly associated with treatment receipt. Patients who were male, older, not married, or smokers had significantly higher risks of death. Chemotherapy was significantly associated with lower mortality for stage III, but not stage II, colon cancer. For rectal cancer, pre-operative radiotherapy was associated with reduced mortality. Surgery and chemotherapy were associated with longer survival for stage IV patients. The observed inequities in treatment and outcomes suggest that there is potential for further dissemination of therapies in routine practice. Improving treatment availability overall, and equity, has the potential to reduce mortality.

Tamoxifen's protection against breast cancer recurrence is not reduced by concurrent use of the SSRI citalopram.

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.

Comorbidity and survival of Danish breast cancer patients from 1995 to 2005.

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.

Patterns of care and effects on mortality for cancers of the oesophagus and gastric cardia: a population-based study.

BACKGROUND: We investigated temporal trends in treatment, and factors influencing treatment receipt and survival, for upper gastrointestinal cancers in routine community-based clinical practice. PATIENTS AND METHODS: Oesophageal and gastric-cardia cancers, diagnosed during the period 1994-2001, were sourced from the National Cancer Registry (Ireland). Analysis was by Joinpoint regression and multivariate logistic and Cox models. RESULTS: Thirty-five percent of patients received surgery, 35% radiotherapy and 24% chemotherapy. Over time chemo- and radiotherapy receipt increased significantly, whilst surgery decreased. Treatment patterns varied by tumour site, histology and stage. Older and/or unmarried patients were significantly less likely to receive treatment. Among surgically treated patients, those aged 70+ had higher mortality. Among both surgical and non-surgical patients, those receiving chemotherapy or radiotherapy had a modest, short-term, survival benefit. CONCLUSIONS: The use of adjuvant therapies is increasing in routine practice. After adjusting for clinical factors, patient-related factors predicted treatment and mortality. Improving equity in gastrointestinal cancer treatment may help improve survival.