[Show abstract][Hide abstract] ABSTRACT: We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2-27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3-11.3) for overweight/obesity, 6.6 % (95 % CI 5.2-8.0) for alcohol consumption, 5.5 % (95 % CI 4.0-7.0) for physical inactivity, 4.6 % (95 % CI 3.3-6.0) for smoking and 3.2 % (95 % CI 1.6-4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle.
Breast Cancer Research and Treatment 06/2015; DOI:10.1007/s10549-015-3447-7 · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method.
In this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation.
In this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects.
Repeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers.
PLoS ONE 05/2015; 10(5):e0127895. DOI:10.1371/journal.pone.0127895 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recurrence rates after inguinal hernia repair have been reduced to a few per cent, since mesh repair has become standard of care. Lightweight meshes reduce post-operative pain and stiffness in open anterior repair, but for endoscopic repair, the discussion about this benefit is ongoing. This study was done to analyse the effects of lightweight mesh versus heavyweight mesh following endoscopic totally extraperitoneal (TEP) hernia repair.
In a single-centre double-blindly randomized clinical trial, 950 patients with unilateral primary inguinal hernia were randomized to undergo endoscopic TEP using either an Ultrapro(®) or a Prolene(®) mesh. Data were collected by validated questionnaires at day 1, day 7, after 6 weeks and after 3 months, and clinical assessment was performed after 3 months. The presence of groin pain after 3 months, defined as an NRS score >3, was evaluated as the primary outcome measure. Secondary outcomes were foreign body feeling and the impact of pain and foreign body feeling on daily activities.
At 3-month follow-up, the incidence of pain (NRS 4-10) was 2 versus 0.9 % in the lightweight and heavyweight mesh group, respectively (p = 0.17). Pain interfered with daily activities in 1.7 % of the lightweight and 1.5 % of heavyweight group. In the lightweight group, 20 % of patients reported a foreign body feeling versus 18 % in the heavyweight group (p = 0.62). No differences between the groups were observed regarding time to return to work, interference with sports and sexual activities, testicular pain and ejaculatory pain. Severe preoperative pain (OR 2.01, 95 % CI 1.21-3.35, p = 0.01) was the only independent predictor of any post-operative pain after 3 months.
Three months after TEP inguinal repair, there were no significant differences between lightweight and heavyweight mesh use regarding the incidence of pain, foreign body feeling or any other endpoint.
[Show abstract][Hide abstract] ABSTRACT: The 70-gene signature (MammaPrint™) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6 % (95 % CI 9.7–15.8) at 10 years, compared to 6.1 % (95 % CI 4.1–8.5) for low-risk patients (n = 561; P P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95 % CI 0.682–0.782) to 0.741 (95 % CI 0.693–0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.
Breast Cancer Research and Treatment 12/2014; 148(3). DOI:10.1007/s10549-014-3188-z · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and HER2 overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI) and/or [18F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 papers, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on ≥5 studies and robustness in subgroup analyses: presence of microcalcifications on mammography (pooled odds ratio (pOR) 3.14, 95% confidence interval (CI): 2.46-4.00) or ultrasound (mass-associated pOR 2.95, 95%CI: 2.34-3.71), branching or fine linear microcalcifications (pOR 2.11, 95%CI: 1.07-4.14) or extremely dense breasts on mammography (pOR 1.37, 95%CI: 1.07-1.76), and washout (pOR 1.57, 95%CI: 1.11-2.21) or fast initial kinetics (pOR 2.60, 95%CI: 1.43-4.73) on MRI. Maximum [18F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference +0.76, 95%CI: 0.10-1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up.
[Show abstract][Hide abstract] ABSTRACT: To calculate the proportion of cancer cases in the Netherlands in 2010 that were attributable to lifestyle factors by using the most recent data.
Lifestyle risk factors studied were tobacco smoking, alcohol consumption, overweight, lack of physical exercise, and six elements of diet (consumption of vegetables, fruit, processed meat and red meat, and calcium and fibre intake). The lifestyle factors were organised so that the group with the highest risk (e.g. smokers) could be compared with the groups with the lowest risk (e.g. ex-smokers, non-smokers). Cut-off points were in line with Dutch public health messages. We obtained prevalence data on risk factors from national databases. Relative risks for the relationship between lifestyle and cancer were based on the international literature. Incidence and mortality data for cancer in 2010 were obtained through the Netherlands Cancer Registry. We calculated percentages of new cancer cases and deaths for men and women and for each type of cancer individually; these were then summed.
We estimated that of the 98,971 newly-diagnosed cases of cancer among persons aged ≥ 20 years in the Netherlands in 2010, 29,938 (30%) were attributable to the above-mentioned lifestyle factors. Smoking was the most important contributory risk factor (19% of all new cancer cases), followed by sub-optimal dietary habits (10%), overweight (4%), alcohol consumption (3%), and lack of physical activity (2%). Of cancer deaths in 2010, an estimated 38% were attributable to lifestyle factors. Projections for 2020 show that lack of exercise and consumption of alcohol and meat will contribute less to the development of cancer while overweight and a reduction in inadequate dietary fibre intake and inadequate fruit and vegetable consumption will contribute more.
Almost one-third of all cases of cancer and almost 40% of deaths from cancer can be attributed to a less healthy lifestyle.
Nederlands tijdschrift voor geneeskunde 01/2014; 159:A8085.
[Show abstract][Hide abstract] ABSTRACT: Undernutrition during critical periods of growth and development may permanently affect lung physiology and function.
To investigate whether acute undernutrition in childhood or young adulthood increases the risk of later hospitalization for obstructive airways disease, chronic obstructive pulmonary disease (COPD), or asthma.
We studied 7,841 women from Prospect-EPIC who experienced the 1944-45 Dutch famine between ages 0 and 21. Pulmonary outcomes were measured by registered hospital admissions and exposure-blinded computed tomography (CT) in a subgroup of 295 women. With Cox proportional hazard regression we explored effects of famine exposure on risk of hospitalization for obstructive airways disease, COPD, and asthma. With logistic regression we explored effects of famine on risk of CT evidence of pulmonary disease.
RISKS OF HOSPITALIZATION FOR OBSTRUCTIVE AIRWAYS DISEASE, COPD, AND ASTHMA WERE INCREASED AFTER MODERATE FAMINE EXPOSURE, AND SIGNIFICANTLY INCREASED AFTER SEVERE FAMINE EXPOSURE: hazard ratios for obstructive airways disease were 1.31 (95% CI: 0.97 to 1.77) and 1.57 (95% CI: 1.10 to 2.23) respectively. Associations between famine exposure and hospitalization for COPD were stronger in ever-smokers than in never-smokers.
Acute undernutrition in childhood or young adulthood is associated with an increased risk of later COPD and asthma hospitalization, possibly through increased sensitivity for tobacco smoke.
PLoS ONE 12/2013; 8(12):e82636. DOI:10.1371/journal.pone.0082636 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Molecular imaging of breast cancer is a promising emerging technology, potentially able to improve clinical care. Valid imaging targets for molecular imaging tracer development are membrane-bound hypoxia-related proteins, expressed when tumor growth outpaces neo-angiogenesis. We performed a systematic literature review and meta-analysis of such hypoxia marker expression rates in human breast cancer to evaluate their potential as clinically relevant molecular imaging targets.
We searched MEDLINE and EMBASE for articles describing membrane-bound proteins that are related to hypoxia inducible factor 1alpha (HIF-1alpha), the key regulator of the hypoxia response. We extracted expression rates of carbonic anhydrase-IX (CAIX), glucose transporter-1 (GLUT1), C-X-C chemokine receptor type-4 (CXCR4), or insulin-like growth factor-1 receptor (IGF1R) in human breast disease, evaluated by immunohistochemistry. We pooled study results using random-effects models and applied meta-regression to identify associations with clinicopathological variables.
Of 1,705 identified articles, 117 matched our selection criteria, totaling 30,216 immunohistochemistry results. We found substantial between-study variability in expression rates. Invasive cancer showed pooled expression rates of 35% for CAIX (95% confidence interval (CI): 26-46%), 51% for GLUT1 (CI: 40-61%), 46% for CXCR4 (CI: 33-59%), and 46% for IGF1R (CI: 35-70%). Expression rates increased with tumor grade for GLUT1, CAIX, and CXCR4 (all p < 0.001), but decreased for IGF1R (p < 0.001). GLUT1 showed the highest expression rate in grade III cancers with 58% (45-69%). CXCR4 showed the highest expression rate in small T1 tumors with 48% (CI: 28-69%), but associations with size were only significant for CAIX (p < 0.001; positive association) and IGF1R (p = 0.047; negative association). Although based on few studies, CAIX, GLUT1, and CXCR4 showed profound lower expression rates in normal breast tissue and benign breast disease (p < 0.001), and high rates in carcinoma in situ. Invasive lobular carcinoma consistently showed lower expression rates (p < 0.001).
Our results support the potential of hypoxia-related markers as breast cancer molecular imaging targets. Although specificity is promising, combining targets would be necessary for optimal sensitivity. These data could help guide the choice of imaging targets for tracer development depending on the envisioned clinical application.
BMC Cancer 11/2013; 13(1):538. DOI:10.1186/1471-2407-13-538 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the effects of famine exposure during childhood on coronary calcium deposition and, secondarily, on cardiac valve and aortic calcifications.
286 postmenopausal women with individual measurements of famine exposure during childhood in the Netherlands during World War II.
Famine exposure during childhood.
Coronary artery calcifications measured by CT scan and scored using the Agatston method; calcifications of the aorta and cardiac valves (mitral and/or aortic) measured semiquantitatively. Logistic regression was used for coronary Agatston score of >100 or ≤100, valve or aortic calcifications as the dependent variable and an indicator for famine exposure as the independent variable. These models were also used for confounder adjustment and stratification based on age groups of 0-9 and 10-17 years.
In the overall analysis, no statistically significant association was found between severe famine exposure in childhood and a high coronary calcium score (OR 1.80, 95% CI 0.87 to 3.78). However, when looking at specific risk periods, severe famine exposure during adolescence was related to a higher risk for a high coronary calcium score than non-exposure to famine, both in crude (OR 3.47, 95% CI 1.00 to 12.07) and adjusted analyses (OR 4.62, 95% CI 1.16 to 18.43). No statistically significant association was found between childhood famine exposure and valve or aortic calcification (OR 1.66, 95% CI 0.69 to 4.10).
Famine exposure in childhood, especially during adolescence, seems to be associated with a higher risk of coronary artery calcification in late adulthood. However, the association between childhood famine exposure and cardiac valve/aortic calcification is less clear.
BMJ Open 11/2013; 3(11):e003818. DOI:10.1136/bmjopen-2013-003818 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery.
From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization) and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration.
348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7%) patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28), number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01), presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77), and microinvasion (OR 3.75, 95% CI 1.42-9.87). The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R (2) ), mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73), and fairly good calibration.
The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.
PLoS ONE 10/2013; 8(10):e77826. DOI:10.1371/journal.pone.0077826 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Desmoid-type fibromatosis is a locally aggressive soft tissue tumour with a biological behaviour that varies between relatively indolent and progressive growth. Although there is a trend towards conservative treatment, surgery remains the standard treatment for extra-abdominal desmoid tumours.
Databases of three hospitals were searched to identify patients who had been treated for desmoid-type fibromatosis between November 1989 and May 2011. The risk of local recurrence was evaluated and predictive factors were assessed in patients who underwent surgical resection as initial treatment for a primary tumour.
A total of 132 patients had surgical treatment for a primary tumour. A complete resection (R0) was achieved in 87 patients (65·9 per cent). In addition to surgery, 54 patients received radiotherapy. During a median follow-up of 38 months, 18 local recurrences were detected. The estimated 5-year cumulative risk of local recurrence was 17·6 per cent. Univariable Cox regression analysis demonstrated that the risk of local recurrence increased for extremity lesions compared with desmoids on the trunk (odds ratio 6·69, 95 per cent confidence interval 1·42 to 31·54). No significant influence of age, resection margins or adjuvant radiotherapy on the risk for local recurrence was observed.
Following surgical treatment of a primary extra-abdominal desmoid tumour, the 5-year risk of local recurrence is modest and not influenced by microscopically clear resection margins or adjuvant radiotherapy.
British Journal of Surgery 06/2013; 100(9). DOI:10.1002/bjs.9194 · 5.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84-0.99) (p < 0.001), 0.81 (95 % CI 0.69-0.93) (p = 0.011), and 0.89 (95 % CI 0.83-0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies.
Breast Cancer Research and Treatment 06/2013; 139(3). DOI:10.1007/s10549-013-2576-0 · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To determine to what extent the Rome III criteria for irritable bowel syndrome can contribute towards safely reducing unnecessary referrals for colonoscopy in primary care patients with lower gastrointestinal (GI) complaints. DESIGN: Data from the CEDAR study were used: a cross-sectional study in 810 patients with lower GI complaints suggestive for organic bowel disease who were referred by their general practitioner for secondary care colonoscopy. Fulfilment of the Rome III criteria was ascertained by a questionnaire. General practitioners recorded the presence or absence of alarm symptoms. Outcome was determined by colonoscopy and histology. RESULTS: Of 810 participants, 222 fulfilled the Rome III criteria [27%, 95% confidence interval (CI) 24-31%]. The majority of these patients presented with alarm symptoms. Only 39 participants fulfilled the Rome III criteria and lacked alarm symptoms (overall frequency 5%, 95% CI 4-7). Overall, organic bowel disease was diagnosed in 141 participants (17%). Participants who fulfilled the Rome III criteria had a significantly lower risk of organic bowel disease compared with participants who did not [12% (95% CI 8-17) vs. 20% (95% CI 17-23), P<0.01]. The lowest risk was observed in patients without alarm symptoms who fulfilled the Rome III criteria (3%, 95% CI 0-14). CONCLUSION: A minority of referred primary care patients with lower GI complaints both fulfilled the Rome III criteria for irritable bowel syndrome and lacked alarm symptoms. Although organic bowel disease could be ruled out safely in this small group, application of the Rome III criteria is not likely to lead to a considerable reduction in unnecessary referrals for colonoscopy in these patients.
European journal of gastroenterology & hepatology 01/2013; DOI:10.1097/MEG.0b013e32835d4ddd · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Since the introduction of the sentinel lymph node biopsy (SLNB) in patients with breast cancer, micrometastases and isolated tumor cells are detected frequently in the SLN. As such, they offer an opportunity to study the development of regional metastases in breast cancer. PATIENTS AND METHODS: Between June 1999 and November 2010 1418 patients with cT1-2N0 breast cancer underwent SLNB. Primary tumor characteristics and information regarding regional lymph node involvement were collected prospectively. Patients were categorized into four levels of lymph node involvement: pN0, pN0(i+), pN1mi and pN ≥ 1a. An univariate analysis and a binary logistic regression analysis were performed to assess the relation between patient- and tumor characteristics and lymph node involvement. RESULTS: Increasing tumor size and younger age were associated with a higher risk of pN1mi and pN ≥ 1a and a lower chance of pN0 and pN0(i+). Triple negative molecular subtype was associated with a decreased risk of pN1mi and pN ≥ 1a. Tumor size was positively related to overall occurrence of regional lymph node metastases in a linear manner. CONCLUSION: Patients with larger tumors, no triple negative disease, and younger age showed a decreased chance of both pN0 and pN0(i+) and an increased risk of both pN1mi and pN ≥ 1a. There seems to be a gradual shift in risk pattern from pN0 to pN0(i+) to pN1mi and to pN ≥ 1a-disease. The presence of the smallest metastases remained fairly constant over time when compared to macrometastases. This constant presence suggests that the risk of seeding and outgrowth of metastases remains constant over time.
Breast (Edinburgh, Scotland) 01/2013; 22(5). DOI:10.1016/j.breast.2012.12.013 · 2.58 Impact Factor