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.

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.

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.

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.

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.

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.

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.

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.