Administration of adjuvant chemotherapy in older patients with Stage III colon cancer: an observational study.

AIM: According to established guidelines, patients with Stage III colon cancer should receive adjuvant chemotherapy. However, a significant proportion do not. This study assessed factors associated with the administration of adjuvant chemotherapy and causes of death. METHODS: Patients with Stage III colon cancer who underwent surgery between 2000 and 2009 were selected from two hospitals in the Netherlands. Patient characteristics including comorbidities and treatment preferences, tumour characteristics and follow-up were extracted from the medical records. The patient and tumour characteristics of patients who did receive chemotherapy were compared with those who did not using chi-squared analysis. Differences between the groups in causes of death were recorded together with the duration of follow-up. RESULTS: A total of 348 patients were included. The median age was 73 years (range 33-93). Over half of the patients received adjuvant chemotherapy (50.6%). Patients who did not receive adjuvant chemotherapy were significantly older (P < 0.001), had more comorbidities (P < 0.001) and were more often living alone (P < 0.001). Patients who received no adjuvant chemotherapy had a reduced overall survival, and the cause of death was more often attributed to other causes (60%) than colon cancer (40%). For patients who received chemotherapy, the cause of death was usually attributed to colon cancer (71%). CONCLUSION: Patients who did not receive adjuvant chemotherapy had a worse overall survival and the majority died due to other causes than colon cancer. In our aging society it will become even more important to develop tools to estimate remaining life expectancy in order to improve the selection of older patients for adjuvant treatments.

Validity of the online PREDICT tool in older patients with breast cancer: a population-based study.

BACKGROUND: Predicting breast cancer outcome in older patients is challenging, as it has been shown that the available tools are not accurate in older patients. The PREDICT tool may serve as an alternative tool, as it was developed in a cohort that included almost 1800 women aged 65 years or over. The aim of this study was to assess the validity of the online PREDICT tool in a population-based cohort of unselected older patients with breast cancer. METHODS: Patients were included from the population-based FOCUS-cohort. Observed 5- and 10-year overall survival were estimated using the Kaplan-Meier method, and compared with predicted outcomes. Calibration was tested by composing calibration plots and Poisson Regression. Discriminatory accuracy was assessed by composing receiver-operator-curves and corresponding c-indices. RESULTS: In all 2012 included patients, observed and predicted overall survival differed by 1.7%, 95% confidence interval (CI)=-0.3-3.7, for 5-year overall survival, and 4.5%, 95% CI=2.3-6.6, for 10-year overall survival. Poisson regression showed that 5-year overall survival did not significantly differ from the ideal line (standardised mortality ratio (SMR)=1.07, 95% CI=0.98-1.16, P=0.133), but 10-year overall survival was significantly different from the perfect calibration (SMR=1.12, 95% CI=1.05-1.20, P=0.0004). The c-index for 5-year overall survival was 0.73, 95% CI=0.70-0.75, and 0.74, 95% CI=0.72-0.76, for 10-year overall survival. CONCLUSIONS: PREDICT can accurately predict 5-year overall survival in older patients with breast cancer. Ten-year predicted overall survival was, however, slightly overestimated.

Both low circulating insulin-like growth factor-1 and high-density lipoprotein cholesterol are associated with hair loss in middle-aged women.

BACKGROUND: Multiple biomarkers have been associated with hair loss in women, but studies have shown inconsistent results. OBJECTIVES: We investigated the associations between markers of cardiovascular disease risk (e.g. serum lipid levels and hypertension) and ageing [e.g. 25-hydroxyvitamin D and insulin-like growth factor (IGF)] with hair loss in a population of middle-aged women. METHODS: In a random subgroup of 323 middle-aged women (mean age 61·5 years) from the Leiden Longevity Study, hair loss was graded by three assessors using the Sinclair scale; women with a mean score > 1·5 were classified as cases with hair loss. RESULTS: Every 1 SD increase in high-density lipoprotein (HDL) cholesterol was associated with a 0·65-times lower risk [95% confidence interval (CI) 0·46-0·91] of hair loss. For IGF-1 the risk was 0·68 times lower (95% CI 0·48-0·97) per 1 SD increase, independently of the other studied variables. Women with both IGF-1 and HDL cholesterol levels below the medians of the study population had a 3·47-times higher risk (95% CI 1·30-9·25) of having hair loss. CONCLUSIONS: Low HDL cholesterol and IGF-1 were associated with a higher risk of hair loss in women. However, further studies are required to infer causal relationships.

Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies.

PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive or actually non-adherent? Therefore, the aim of this study was to describe, within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), characteristics of both non-responders and high responders of statin treatment in order to possibly discriminate non-responders from non-adherers. METHODS: Baseline characteristics of non-responders to statin therapy (≤10 % LDL-C reduction) were compared with those of high responders (>40 % LDL-C reduction) through a linear regression analysis. In addition, pharmacogenetic candidate gene analysis was performed to show the effect of excluding non-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p < 0.001), had a higher alcohol consumption (p < 0.001), had lower LDL cholesterol levels (p < 0.001), had a lower prevalence of hypertension (p < 0.001), and had lower cognitive function (p = 0.035) compared to subjects who highly responded to pravastatin treatment. Moreover, excluding non-responders from pharmacogenetic studies yielded more robust results, as standard errors decreased. CONCLUSION: Our results suggest that non-responders to statin therapy are more likely to actually be non-adherers, since they have more characteristics that are viewed as indicators of high self-perceived health and low disease awareness, possibly making the subjects less adherent to study medication. We suggest that in pharmacogenetic research, extreme non-responders should be excluded to overcome the problem that non-adherence is investigated instead of non-responsiveness.

Contralateral breast cancer risk in relation to tumor morphology and age-in which patients is preoperative MRI justified?

Identification of patients who are at increased risk for contralateral breast cancer is essential to determine which patients should be routinely screened for contralateral breast cancer using MRI. The aim of this study was to assess the association of age and tumor morphology with contralateral breast cancer incidence in a large, nationwide population-based study in the Netherlands. All patients with breast cancer stage I-III, diagnosed between 1989 and 2009, were selected from the Netherlands Cancer Registry. The association between contralateral breast cancer risk with tumor morphology and age was assessed using competing-risk regression according to Fine & Gray. Overall, 194,898 patients were included. In multivariable analyses, lobular tumors were significantly associated with an increased risk of contralateral breast cancer within 6 months (cumulative incidence 1.9 %, subdistribution hazard ratio (SHR) 1.17, 95 % confidence interval (CI) 1.06-1.30 compared with 1.3 % in ductal tumors, p = 0.002). Age was also associated with an increased risk of contralateral breast cancer within 6 months (SHR 2.34, 95 % CI 2.08-2.62, p < 0.002 for patients over the age of 75 as compared to patients younger than 50 years). The absolute risk of contralateral breast cancer within 6 months is only slightly increased in patients with a lobular tumor and older patients. In our view, this small increased risk does not justify standard use of preoperative MRI based on tumor morphology or age alone. We propose a more personalized strategy in which additional risk factors (family history, prognosis of primary tumor, and others) may play a role.

Lifestyle and youthful looks.

BACKGROUND: Lifestyle has been proven to have a dramatic effect on the risk of age-related diseases. The association of lifestyle and facial ageing has been less well studied. OBJECTIVES: To identify lifestyle factors that associate with perceived facial age in white north European men and women. METHODS: Lifestyle, facial wrinkling and perceived facial age were studied in two cross-sectional studies consisting of 318 Dutch men and 329 women aged 45-75 years who were part of the Leiden Longevity Study, and 162 English women aged 45-75 years who were nonsmokers. RESULTS: In Dutch men, smoking, having skin that went red in the sun, being outside in the sun most of the summer, sunbed use, wearing false teeth and not flossing teeth were all significantly associated (P < 0·05) with a total 9·3-year higher perceived facial age in a multivariate model adjusting for chronological age. In Dutch women, smoking, sunbathing, sunbed use, few remaining teeth and a low body mass index (BMI) were associated with a total 10·9-year higher perceived facial age. In English women, cleaning teeth only once a day, wearing false teeth, irregular skin moisturization and having skin that went red in the sun were associated with a total 9·1-year higher perceived facial age. Smoking and sunbed use were associated more strongly with wrinkling in women than in men. BMI, sun exposure and skincare were associated predominantly with perceived facial age via wrinkling, whereas oral care was associated via other facial features. CONCLUSIONS: Although associative in nature, these results support the notion that lifestyle factors can have long-term beneficial effects on youthful looks.

In depressed older persons higher blood pressure is associated with symptoms of apathy. The NESDO study.

BACKGROUND: In older persons, a relationship between both higher and lower blood pressure and depression has inconsistently been reported. Blood pressure may be differentially associated with distinct symptom domains of depression. We examined the cross-sectional relation of current systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) with different depressive symptom domains among depressed older persons. METHODS: In the Netherlands Study of Depression in Older Persons (NESDO), 270 participants aged 60 years and above were diagnosed with depression in the past month. Using the three corresponding subscales of the Inventory of Depressive Symptoms-Self Report (IDS-SR), motivational, mood and somatic symptom domains were assessed. Additionally, symptoms of apathy were determined with the Apathy Scale. Multiple linear regression was used to examine the cross-sectional relationship between current SBP, DBP and MAP with both IDS-SR subscale and Apathy Scale scores. Unstandardized betas were calculated per 10 mmHg increase in blood pressure measures. RESULTS: Mean age of participants was 70.4 years (standard deviation 7.3). Higher SBP (Beta 0.33, t (254) = 2.01, p = 0.045), higher DBP (Beta 0.68, t (254) = 2.15, p = 0.03) and higher MAP (Beta 0.63, t (254) = 2.33, p = 0.02) were associated with higher Apathy Scale scores in the fully adjusted model. Furthermore, a higher SBP was associated with higher IDS-SR mood subscale scores (Beta 0.25, t (254) = 2.13, p = 0.03). CONCLUSIONS: Depressed older people with higher blood pressure measures had particularly more symptoms of apathy. To disentangle the relationship of blood pressure with late-life depression, it is important to pay attention to the role of apathy symptoms.

Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment.

With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of older patients. The aim of this study was to present an overview of trial characteristics and endpoints of all currently running clinical trials in breast cancer, particularly in older patients. The clinical trial register of the United States National Institutes of Health Differences was searched for all current clinical trials on breast cancer treatment. Trial characteristics and endpoints were retrieved from the register and differences in characteristics between studies in older patients specifically (defined as a lower age-limit of 60 years or older) and trials in all patients were assessed using χ(2) tests. We included 463 clinical trials. Nine trials (2 %) specifically investigated breast cancer treatment in older patients. Ninety-one breast cancer trials included any patient-related endpoint (20 %), while five trials specifically addressing older patients included any patient-related endpoint (56 %, P = 0.02). Five of the trials in older patients incorporated a geriatric assessment (56 %). Clinical trials still rarely incorporate patient-related endpoints, even in trials that specifically address older patients. Trials that are specifically designed for older patients do not often incorporate a geriatric assessment in their design. This implicates that current clinical studies are not expected to fill the gap in knowledge concerning treatment of older breast cancer patients in the next decade.

Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.

Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.

Impact of omission of surgery on survival of older patients with breast cancer.

BACKGROUND: Older patients with breast cancer are often not treated in accordance with guidelines. With the emergence of endocrine therapy, omission of surgery can be considered in some patients. The aim of this population-based study was to investigate time trends in surgical treatment between 1995 and 2011, and to evaluate the effects of omitting surgery on overall and relative survival in older patients with resectable breast cancer. METHODS: Patients aged 75 years and older with stage I-III breast cancer diagnosed between 1995 and 2011 were selected from the Netherlands Cancer Registry. Time trends of all treatment modalities were evaluated using linear regression models. Changes in overall survival were calculated by Cox regression. Relative survival was calculated using the Ederer II method. RESULTS: Overall, 26 292 patients were included. The proportion of patients receiving surgical treatment decreased significantly, from 90·8 per cent in 1995 to 69·9 per cent in 2011 (P < 0·001). Multivariable analysis showed that overall survival did not change over time (hazard ratio 1·00 (95 per cent confidence interval (c.i.) 0·99 to 1·00) per year); nor did relative survival (relative excess risk 1·00 (0·98 to 1·02) per year). CONCLUSION: Omission of surgery has become more common in older patients with breast cancer during the past 15 years in the Netherlands, but this has not altered overall or relative survival.

Using genetic variation for establishing causality of cardiovascular risk factors: overcoming confounding and reverse causality.

Cardiovascular disease (CVD) remains the leading cause of death in developed countries, despite the decline of CVD mortality over the last two decades. From observational, predictive research, efforts have been made to find causal risk factors for CVD. However, in recent years, some of these findings have been shown to be mistaken. Possible explanations for the discrepant findings are confounding and reverse causation. Genetic epidemiology has tried to address these problems through the use of Mendelian randomisation. In this paper, we discuss the promise and limitations of using genetic variation for establishing causality of cardiovascular risk factors.

Diabetes in relation to breast cancer relapse and all-cause mortality in elderly breast cancer patients: a FOCUS study analysis.

BACKGROUND: In developed countries, 40% of breast cancer patients are >65 years of age at diagnosis, of whom 16% additionally suffer from diabetes. The aim of this study was to assess the impact of diabetes on relapse-free period (RFP) and overall mortality in elderly breast cancer patients. PATIENTS AND METHODS: Patients were selected from the retrospective FOCUS cohort, which contains detailed information of elderly breast cancer patients. RFP was calculated using Fine and Gray competing risk regression models for patients with diabetes versus patients without diabetes. Overall survival was calculated by Cox regression models, in which patients were divided into four groups: no comorbidity, diabetes only, diabetes and other comorbidity or other comorbidity without diabetes. RESULTS: Overall, 3124 patients with non-metastasized breast cancer were included. RFP was better for patients with diabetes compared with patients without diabetes (multivariable HR 0.77, 95% CI 0.59-1.01), irrespective of other comorbidity and most evident in patients aged ≥75 years (HR 0.67, 95% CI 0.45-0.98). The overall survival was similar for patients with diabetes only compared with patients without comorbidity (HR 0.86, 95% CI 0.45-0.98), while patients with diabetes and additional comorbidity had the worst overall survival (HR 1.70, 95% CI 1.44-2.01). CONCLUSION: When taking competing mortality into account, RFP was better in elderly breast cancer patients with diabetes compared with patients without diabetes. Moreover, patients with diabetes without other comorbidity had a similar overall survival as patients without any comorbidity. Possibly, unfavourable effects of (complications of) diabetes on overall survival are counterbalanced by beneficial effects of metformin on the occurrence of breast cancer recurrences.

Postoperative complications and survival of elderly breast cancer patients: a FOCUS study analysis.

Old age is associated with comorbidity and decreased functioning which influences treatment decisions in elderly breast cancer patients. The purpose of this study was to identify risk factors for complications after breast cancer surgery in elderly patients, and to assess mortality in patients with postoperative complications. The FOCUS cohort is a detailed retrospective cohort of all breast cancer patients aged 65 years and older who were diagnosed between 1997 and 2004 in the South-West of the Netherlands. Risk factors for postoperative complications were assessed using univariable and multivariable logistic regression models. One-year survival and overall survival were calculated using univariable and multivariable Cox Regression models, and relative survival was calculated according to the Ederer II method. 3179 patients received surgery, of whom 19 % (n = 618) developed 1 or more postoperative complication(s). The odds ratio of having postoperative complications increased with age [OR 1.85 (95 % confidence interval (CI) 1.37-2.50, p = 0.001) in patients >85 years] and number of concomitant diseases [OR 1.71 (95 % CI 1.30-2.24, p ≤ 0.001) for 4 or more concomitant diseases]. One-year overall survival, overall survival, and relative survival were worse in patients with postoperative complications [multivariable HR 1.49 (95 % CI 1.05-2.11), p = 0.025. HR 1.21, (95 % CI 1.07-1.36), p = 0.002 and RER 1.19 (95 % CI 1.05-1.34), p = 0.006 respectively]. Stratified for comorbidity, relative survival was lower in patients without comorbidity only. Increasing number of concomitant disease increased the risk of postoperative complications. Although elderly patients with comorbidity did have a higher risk of postoperative complications, relative mortality was not higher in this group. This suggests that postoperative complications in itself did not lead to higher relative mortality, but that the high relative mortality was most likely due to geriatric parameters such as comorbidity or poor physical function.

Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study.

BACKGROUND: Inflammation is involved in the pathogenesis of cardiovascular disease and cognitive decline. Interleukin-6 (IL-6) has a role in cardiovascular disease, but the association of IL-6 concentration and the functional IL-6 -174 polymorphism with cognitive decline has not been demonstrated unequivocally. The objective of this study was to investigate the associations between both high concentration of IL-6 and the -174 promoter polymorphism, and increased cognitive decline in old age. METHODS: Over 5000 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with a mean age of 75 years and a history of cardiovascular disease or its risk factors were included in this study. We determined baseline concentrations of IL-6 and genotype of the IL-6 -174 polymorphism, of which the C allele was previously shown to be associated with higher circulating concentrations of IL-6. A cognitive test battery was administered at baseline and repeatedly during follow-up (mean 39 months). RESULTS: In the cross-sectional analysis of 5653 participants, higher IL-6 concentration was associated with worse executive cognitive function (P < 0.001), independent of cardiovascular disease status and risk factors. No association was found between IL-6 concentration and memory function (P > 0.14). In the prospective analysis, higher IL-6 concentration was associated with an increased rate of cognitive decline in both executive function (P = 0.002) and memory function (P = 0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL-6 concentrations, the IL-6 -174 CC genotype was associated with worse performance on the Stroop test (P = 0.045). CONCLUSIONS: Higher circulating levels of IL-6 were associated with worse cognitive function and steeper cognitive decline and provide preliminary genetic evidence for a potential causal association. The findings support the importance of the need for further investigation of the IL-6 pathway in cognitive decline.

Serum insulin-like growth factor 1 and facial ageing: high levels associate with reduced skin wrinkling in a cross-sectional study.

BACKGROUND: Insulin-like growth factor (IGF)-1 is a growth factor that can influence fibroblast functioning, with effects including the inhibition of collagenases and the induction of collagen expression. OBJECTIVES: To assess whether serum IGF-1, IGF-binding protein (IGFBP)3 and the ratio between IGF-1 and IGFBP3, as a measure of IGF-1 bioavailability, are associated with facial ageing and skin wrinkling. METHODS: From a random sample comprising 617 subjects from the Leiden Longevity Study, perceived age and skin wrinkling were assessed from facial photographs, and IGF-1 and IGFBP3 were measured in serum. The associations were assessed using linear regression models, adjusted for chronological age, sex, body mass index, smoking and sun exposure. RESULTS: Across tertiles of the ratio of IGF-1 to IGFBP3, and after adjusting for all potential confounding factors, the mean perceived age decreased from 60·6 years in the lowest tertile to 59·5 years in the highest (P = 0·045). Similarly, the mean skin wrinkling grade decreased from 4·8 in the lowest tertile to 4·5 in the highest (P = 0·011). Adding skin wrinkling as a covariate in the analysis between IGF-1 and perceived age diminished this association. CONCLUSIONS: This study demonstrates that a higher ratio of IGF-1 to IGFBP3 associates with a lower perceived age, via its association with reduced skin wrinkling. Whether high IGF-1 levels actually delay the accumulation of skin wrinkling now needs investigating.

Use of aspirin postdiagnosis improves survival for colon cancer patients.

BACKGROUND: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. METHODS: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998-2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. RESULTS: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63-0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50-0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46-0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79-1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70-2.20; P<0.001). CONCLUSION: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of a placebo-controlled trial that investigates the role of aspirin as adjuvant treatment in colon cancer patients.

Surgical treatment of early stage breast cancer in elderly: an international comparison.

Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥ 65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

Adherence to treatment guidelines and survival in patients with early-stage breast cancer by age at diagnosis.

BACKGROUND: Elderly patients with breast cancer are under-represented in clinical studies. It is not known whether treatment guidelines, based on clinical trials, can be extrapolated to this population. The aim of this study was to assess adherence to treatment guidelines by age at diagnosis, and to examine age-specific survival in relation to adherence to guidelines. METHODS: Patients with early-stage breast cancer aged either less than 65 years, or 75 years or more, diagnosed between 2005 and 2008, were identified from the Netherlands Cancer Registry. Adherence to treatment guidelines for breast and axillary surgery, radiotherapy, chemotherapy and endocrine therapy was determined. Non-adherence to the guidelines was defined as overtreatment or undertreatment. The primary endpoint was overall survival, assessed by means of an instrumental variable, the comprehensive cancer centre region. RESULTS: Some 24 959 patients younger than 65 years and 6561 patients aged 75 years or more were included in the analysis. Median follow-up was 2·8 years. Compared with patients younger than 65 years, those aged at least 75 years were less frequently treated in concordance with guidelines: 62·0 per cent (15 487 patients) versus 55·6 per cent (3647 patients) (P < 0·001). In both age groups, most patients received at least three of five treatment modalities in concordance with guidelines: 98·8 per cent (24 652 patients) and 93·8 per cent (6152 patients) respectively. Analysis of survival using the instrumental variable showed that adherence to guidelines was not associated with overall survival in patients younger than 65 years (P = 0·601) or those aged at least 75 years (P = 0·190). CONCLUSION: Adherence to treatment guidelines was affected by age at diagnosis. However, adherence to the guidelines was not associated with overall survival in either age group.

Socioeconomic differences in survival among breast cancer patients in the Netherlands not explained by tumor size.

There seem to be socioeconomically differences in survival for females with breast cancer, usually associated with a higher stage of disease. However, differences within tumor size have not been studied. Aim of this study is to assess differences in survival according to socioeconomic status (SES), stratified for tumor size and stage at diagnosis, for females with breast cancer in the Netherlands. All females diagnosed with breast cancer (1995-2005) were selected from the Netherlands Cancer Registry. Patients were linked to a SES database according to postal code. A multivariable logistic regression was used to assess factors associated with SES. Overall survival (OS) and relative survival (RS) were calculated. Overall, 127,599 patients were included. Higher SES was associated with lower T-stage (P < 0.0001). A decreased survival (OS and RS) was found for patients with a lower SES. Also within different size groups, RS was different. Overall, 10-year OS for the high SES group was 65 and 58% for the low SES group (hazard ratio 1.1, P < 0.001) and RS was 79 versus 74% (relative excess risk, RER 1.2; P < 0.001). The socioeconomic differences remained statistically significant (P < 0.001) after adjustment for age, year of diagnosis, grade, TNM stage, and treatment. For the lowest SES group 777 deaths could be avoided. Socioeconomic differences in survival of breast cancer patients were observed in the Netherlands. Higher stage at diagnosis of patients with a lower SES only partly explains the decreased survival. Policies aimed at the reduction of socioeconomic health inequalities might be important to improve survival of breast cancer.

Breast cancer in elderly compared to younger patients in the Netherlands: stage at diagnosis, treatment and survival in 127,805 unselected patients.

Breast cancer is the most common type of cancer in several parts of the world and the number of elderly patients is increasing. The aim of this study was to describe stage at diagnosis, treatment, and relative survival of elderly patients compared to younger patients in the Netherlands. Adult female patients with their first primary breast cancer diagnosed between 1995 and 2005 were selected. Stage, treatment, and relative survival were described for young and elderly (≥ 65 years) patients and within the cohort of elderly patients according to 5-year age groups. Overall, 127,805 patients were included. Elderly breast cancer patients were diagnosed with a higher stage of disease. Moreover, within the elderly differences in stage were observed. Elderly underwent less surgery (99.2-41.2%); elderly received hormonal treatment as monotherapy more frequently (0.8-47.3%); and less adjuvant systemic treatment (79-53%). Elderly breast cancer patients with breast cancer had a decreased relative survival. Although relative survival was lower in the elderly, the percentage of patients who die of their breast cancer less than 50% above age 75. In conclusion, the relative survival for the elderly is lower as compared to their younger counterparts while the percentage of deaths due to other causes increases with age. This could indicate that the patient selection is poor and fit patients could suffer from "under treatment". In the future, specific geriatric screening tools are necessary to identify fit elderly patients who could receive more "aggressive" treatment while best supportive care should be given to frail elderly patients.