Evelyn M. Monninkhof

Physical activity and breast cancer: a systematic review.

Background: Many epidemiologic studies have found an association between physical activity and breast cancer risk, although this has not been a consistent finding. Methods: Studies were identified through a systematic review of literature available on PubMed through February 2006. We included all cohort and case–control studies that assessed total or leisure time activities in relation to occurrence or mortality of breast cancer. The fully adjusted risk estimates and 95% confidence intervals for the highest versus lowest level of activity were documented for each study as well as evidence for a dose–response relationship. Methodologic quality was also assessed. Due to statistical and methodologic heterogeneity among studies, we did not carry out statistical pooling. To draw conclusions, we performed a best-evidence synthesis taking study quality into account. Results: Nineteen cohort studies and 29 case–control studies were evaluated. There was strong evidence for an inverse association between physical activity and postmenopausal breast cancer with risk reductions ranging from 20% to 80%. For premenopausal breast cancer, however, the evidence was much weaker. For pre- and postmenopausal breast cancer combined, physical activity was associated with a modest (15–20%) decreased risk. Evidence for a dose–response relationship was observed in approximately half of the higher-quality studies that reported a decreased risk. A trend analysis indicated a 6% (95% confidence interval = 3% to 8%) decrease in breast cancer risk for each additional hour of physical activity per week assuming that the level of activity would be sustained. Conclusions: There is evidence for an inverse association between physical activity and breast cancer risk. The evidence is stronger for postmenopausal breast cancer than for premenopausal breast cancer.

Physical Activity and Risk of Colon and Rectal Cancers: The European Prospective Investigation into Cancer and Nutrition

We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospective Investigation into Nutrition and Cancer. This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up. We analyzed baseline data on occupational, household, and recreational activity to examine associations by type of activity, tumor subsite, body mass index (BMI), and energy intake. The multivariate hazard ratio for colon cancer was 0.78 [95% confidence interval (95% CI), 0.59-1.03] among the most active participants when compared with the inactive, with evidence of a dose-response effect (Ptrend = 0.04). For right-sided colon tumors, the risk was 0.65 (95% CI, 0.43-1.00) in the highest quartile of activity with evidence of a linear trend (Ptrend = 0.004). Active participants with a BMI under 25 had a risk of 0.63 (95% CI, 0.39-1.01) for colon cancer compared with the inactive. Finally, an interaction between BMI and activity (Pinteraction = 0.03) was observed for right-sided colon cancers; among moderately active and active participants with a BMI under 25, a risk of 0.38 (95% CI, 0.21-0.68) was found as compared with inactive participants with BMI >30. No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered. We found that physical activity reduced colon cancer risk, specifically for right-sided tumors and for lean participants, but not rectal cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2398–407)

Physical Activity and Breast Cancer Risk: The European Prospective Investigation into Cancer and Nutrition

There is convincing evidence for a decreased risk of breast cancer with increased physical activity. Uncertainties remain, however, about the role of different types of physical activity on breast cancer risk and the potential effect modification for these associations. We used data from 218,169 premenopausal and postmenopausal women from nine European countries, ages 20 to 80 years at study entry into the European Prospective Investigation into Cancer and Nutrition. Hazard ratios (HR) from multivariate Cox regression models were calculated using metabolic equivalent value–based physical activity variables categorized in quartiles, adjusted for age, study center, education, body mass index, smoking, alcohol use, age at menarche, age at first pregnancy, parity, current oral contraceptive use, and hormone replacement therapy use. The physical activity assessment included recreational, household, and occupational activities. A total physical activity index was estimated based on cross-tabulation of these separate types of activity. During 6.4 years of follow-up, 3,423 incident invasive breast cancers were identified. Overall, increasing total physical activity was associated with a reduction in breast cancer risk among postmenopausal women (Ptrend = 0.06). Specifically, household activity was associated with a significantly reduced risk in postmenopausal (HR, 0.81; 95% confidence interval, 0.70-0.93, highest versus the lowest quartile; Ptrend = 0.001) and premenopausal (HR, 0.71; 95% confidence interval, 0.55-0.90, highest versus lowest quartile; Ptrend = 0.003) women. Occupational activity and recreational activity were not significantly related to breast cancer risk in both premenopausal and postmenopausal women. This study provides additional evidence for a protective effect of physical activity on breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(1):36–42)

Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: A systematic review

BACKGROUND As neoadjuvant chemotherapy (NAC) is increasingly used to downstage patients with breast cancer, the timing of the sentinel node (SN) biopsy has become an important issue. This review was conducted to determine the accuracy of SN biopsy following NAC. METHODS We searched Medline, Embase and Cochrane databases from 1993 to February 2009 for studies on patients with invasive breast cancer who underwent SN biopsy after NAC followed by an axillary lymph node dissection (ALND). RESULTS Of 574 eligible studies, 27 were included in this review with a total study population of 2148 patients. The pooled SN identification rate was 90.9% (95% confidence interval (CI)=88.0-93.1%) and the false-negative rate was 10.5% (95% CI=8.1-13.6%). Negative predictive value and accuracy after NAC were 89.0% (95% CI=85.1-92.1%) and 94.4% (95% CI=92.6-95.8%), respectively. The reported SN success rates were heterogeneous and several variables were reported to be associated with decreased SN accuracy, i.e. initially positive clinical nodal status. CONCLUSIONS There is a potential role for SN biopsy following NAC which could be considered on an individual basis. However, there is insufficient evidence to recommend this as a standard procedure. Further research with subgroup analysis using variables reported to be associated with decreased SN accuracy is required in order to clearly define its value in the subgroups of breast cancer patients.

Cohort Profile: The EPIC-NL study

A major scientific challenge for the next few decades is to understand the interaction between genetic susceptibility and environmental factors in the aetiology of chronic diseases. The most promising approach to discover these interactions requires a combined effort of epidemiology and molecular genetics and large sample sizes for sufficient power. Already in the early 90s, the European Prospective Investigation Into Cancer and Nutrition (EPIC) was initiated in 10 European countries to create a large cohort to study the aetiology of chronic diseases. The Netherlands has contributed two cohort studies to EPIC: the Prospect cohort of 17 357 women of the Julius Center in Utrecht, and the Monitoring Project on Risk Factors for Chronic Diseases (MORGEN) cohort of 22 654 men and women of the National Institute for Public Health and the Environment (RIVM) in Bilthoven. In the design phase, both cohorts collaborated closely to obtain maximal synergy in the design of the questionnaires and to follow identical protocols in the collection of biological samples. Because of the efficiency gain in maintaining the cohort infrastructure and in conducting scientific analyses, the Julius Center and the RIVM decided to combine efforts to maintain and expand the cohorts and biobanks by merging them into one EPICNetherlands (EPIC-NL) study.

Physical Activity and Mortality in Individuals With Diabetes Mellitus: A Prospective Study and Meta-analysis.

BACKGROUND Physical activity (PA) is considered a cornerstone of diabetes mellitus management to prevent complications, but conclusive evidence is lacking. METHODS This prospective cohort study and meta-analysis of existing studies investigated the association between PA and mortality in individuals with diabetes. In the EPIC study (European Prospective Investigation Into Cancer and Nutrition), a cohort was defined of 5859 individuals with diabetes at baseline. Associations of leisure-time and total PA and walking with cardiovascular disease (CVD) and total mortality were studied using multivariable Cox proportional hazards regression models. Fixed- and random-effects meta-analyses of prospective studies published up to December 2010 were pooled with inverse variance weighting. RESULTS In the prospective analysis, total PA was associated with lower risk of CVD and total mortality. Compared with physically inactive persons, the lowest mortality risk was observed in moderately active persons: hazard ratios were 0.62 (95% CI, 0.49-0.78) for total mortality and 0.51 (95% CI, 0.32-0.81) for CVD mortality. Leisure-time PA was associated with lower total mortality risk, and walking was associated with lower CVD mortality risk. In the meta-analysis, the pooled random-effects hazard ratio from 5 studies for high vs low total PA and all-cause mortality was 0.60 (95% CI, 0.49-0.73). CONCLUSIONS Higher levels of PA were associated with lower mortality risk in individuals with diabetes. Even those undertaking moderate amounts of activity were at appreciably lower risk for early death compared with inactive persons. These findings provide empirical evidence supporting the widely shared view that persons with diabetes should engage in regular PA.

Non–Sentinel Lymph Node Metastases Associated With Isolated Breast Cancer Cells in the Sentinel Node

There are many reports on the frequency of non-sentinel lymph node involvement when isolated tumor cells are found in the sentinel node, but results and recommendations for the use of an axillary lymph node dissection differ among studies. This systematic review was conducted to give an overview of this issue and to provide recommendations for the use of an axillary lymph node dissection in these patients. We searched Medline, Embase, and Cochrane databases from January 1, 2002, through November 27, 2007, for articles on patients with invasive breast cancer who had isolated tumor cells in the sentinel lymph node (according to the sixth edition of the Cancer Staging Manual of the American Joint Committee on Cancer) and who also underwent axillary lymph node dissection. Of 411 selected articles, 29 (including 836 patients) were included in this review. These 29 studies were heterogeneous, reporting a wide range of non-sentinel lymph node involvement (defined as the presence of isolated tumor cells or micro- or macrometastases) associated with isolated tumor cells in the sentinel lymph node, with an overall pooled risk for such involvement of 12.3% (95% confidence interval = 9.5% to 15.7%). This pooled risk estimate was marginally higher than the risk of a false-negative sentinel lymph node biopsy examination (ie, 7%-8%) but marginally lower than the risk of non-sentinel lymph node metastases in patients with micrometastases (ie, approximately 20%) who are currently eligible for an axillary lymph node dissection. Because 36 (64%) of the 56 patients with isolated tumor cells in their sentinel lymph node also had non-sentinel lymph node macrometastases, those patients with isolated tumor cells in the sentinel lymph node without other indications for adjuvant systemic therapy might be candidates for axillary lymph node dissection.

Physical Activity and Endometrial Cancer Risk, a Systematic Review of Current Evidence

Objective: To assess the epidemiologic evidence for the association between physical activity and endometrial cancer risk, taking into account the methodologic quality of each study. Design: Systematic review, best evidence synthesis. Data Sources: Studies were identified through a systematic review of literature available on PubMed through December 2006. Review Methods: We included cohort and case-control studies that assessed total and/or leisure time and/or occupational activities in relation to the incidence of endometrial cancer. The methodologic quality of the studies was assessed with a comprehensive scoring system. Results: The included cohort (n = 7) and case-control (n = 13) studies consistently show that physical activity is associated with a decreased risk of endometrial cancer. The best evidence synthesis showed that the majority (80%) of 10 high-quality studies found risk reductions of >20%. Pooling of seven high-quality cohort studies that measured total, leisure time, or occupational activity showed a significantly decreased risk of endometrial cancer (summary estimate: OR, 0.77; 95% CI, 0.70-0.85) for the most active women. Case control studies with relatively unfavorable quality scores reported divergent risk estimates, between 2-fold decreased and 2-fold increased risk. Effect modification by body mass index or menopausal status was not consistently observed. Evidence for an effect of physical activity during childhood or adolescence was limited. Conclusions: Physical activity seems to be associated with a reduction in the risk of endometrial cancer, which is independent of body weight. Further studies, preferably prospective cohort studies, are needed to determine the magnitude of the risk reduction and to assess which aspects of physical activity contribute most strongly to the reduced risk and in which period of life physical activity is most effective. (Cancer Epidemiol Biomarkers Prev 2007;16(4):639–48)

Effect of an action plan with ongoing support by a case manager on exacerbation-related outcome in patients with COPD: a multicentre randomised controlled trial

Background An individualised action plan (AP) is a potentially effective method of helping patients with chronic obstructive pulmonary disease (COPD) to recognise and anticipate early exacerbation symptoms. This multicentre randomised controlled trial evaluates the hypothesis that individualised APs reduce exacerbation recovery time. Methods Two hundred and thirty-three patients with COPD (age 65±10 years, forced expiratory volume in 1 s 56±21% predicted) were randomised to receive either an individualised AP (n=111) or care as usual (n=122). The AP provides individualised treatment prescriptions (pharmaceutical and non-pharmaceutical) related to a colour-coded symptom status to enhance an adequate response to periods of symptom deterioration (reinforced at 1 and 4 months). Exacerbation onset was defined using the Anthonisen symptom diary card algorithm. Every 3 days the Clinical COPD Questionnaire (CCQ) was assessed to evaluate the longitudinal course of health status. The primary outcome was health status recovery in the event of an exacerbation. Results During the 6-month follow-up period there was no difference in exacerbation rates and healthcare utilisation between the two groups. Cox-adjusted survival analysis including frailty showed enhanced health status recovery (HR 1.58; 95% CI 0.96 to 2.60) and reduced length of the exacerbation (HR 1.30; 95% CI 0.92 to 1.84). The mean difference in symptom recovery time was −3.68 days (95% CI −7.32 to −0.04). Mixed model repeated measure analysis showed that an AP decreased the impact of exacerbations on health status both in the prodromal and early post-onset periods. Between-group differences in CCQ scores were above the minimal clinically relevant difference of 0.4 points (3.0±0.7 vs 3.4±0.9; p≤0.01). Conclusion This study shows that an individualised AP, including ongoing support by a case manager, decreases the impact of exacerbations on health status and tends to accelerate recovery. APs can be considered a key component of self-management programmes in patients with COPD.

Effect of Exercise on Postmenopausal Sex Hormone Levels and Role of Body Fat: A Randomized Controlled Trial

PURPOSE To examine the effects of a 1-year exercise intervention on sex hormone levels in postmenopausal women and whether any effects are mediated by changes in body fat composition. METHODS We randomly assigned 189 sedentary postmenopausal women (age 50 to 69 years, body mass index of 22 to 40 kg/m(2)) to an exercise intervention (n = 96) or a control group (n = 93). The intervention combined aerobic and strength training and comprised supervised group sessions and home-based exercises (a total of 2.5 h/wk). Between-group differences in sex hormone levels (at baseline and 4 and 12 months) were examined with generalized estimating equations. RESULTS In total, 183 women (97%) completed the study. Overall, the exercise intervention did not result in favorable effects on sex hormone levels. Among women who lost more than 2% body fat, declines in all estrogens were not significantly different between exercisers and controls. Androgen levels decreased significantly in the exercise group who lost body fat compared with their peers in the control group. Furthermore, this study confirmed that fat loss was significantly associated with declines in postmenopausal estrogen levels. Although not significant, a similar trend was observed for the androgens. CONCLUSION This study confirms that fat loss is associated with changes in postmenopausal sex hormone levels and suggests that exercise may be effective in inducing favorable changes in these hormones.