Martina E. Schmidt

Fatigue and quality of life in breast cancer survivors: temporal courses and long-term pattern.

IntroductionFatigue is a frequent problem during and after cancer treatment. We investigated different courses of fatigue from pre-diagnosis, through therapy, to long-term survivorship and evaluated potential implications on long-term quality of life (QoL).MethodsBreast cancer patients diagnosed in 2001–2005 were recruited in a case–control study in Germany (MARIE). At follow-up in 2009 (median 5.8xa0years, MARIEplus), patients self-reported current fatigue and QoL status using validated questionnaires (FAQ, EORTC QLQ-C30). In addition, survivors retrospectively rated fatigue levels pre-diagnosis, during different treatment phases, and 1xa0year post-surgery. Our analyses included 1,928 disease-free cancer survivors and comparisons with fatigue and QoL scores from the general population.ResultsFatigue levels were substantially increased during chemotherapy and radiotherapy. Among patients who received both therapies, 61.4% reported higher, 30.0% same, and 8.6% lower fatigue levels during chemotherapy compared to radiotherapy. Courses of fatigue varied widely between individuals. Survivors with persisting long-term fatigue had significantly and markedly worse scores for all QoL functions and symptoms about 6xa0years post-diagnosis than other survivors and compared to the general population. Survivors without substantial fatigue post-treatment had QoL scores largely comparable to the general population.Discussions/conclusionChemotherapy appears to have a stronger impact on fatigue than radiotherapy. Breast cancer survivors may experience long-term QoL comparable to the general population, even when suffering from substantial fatigue during treatment. Yet, persistent fatigue post-treatment may lead to extensive long-term loss in QoL concerning physical, social, cognitive, and financial aspects.Implications for cancer survivorsFatigue management should be obligatory during and post cancer treatment.

Physical Activity and Postmenopausal Breast Cancer: Effect Modification by Breast Cancer Subtypes and Effective Periods in Life

Physical activity (PA) has been inversely associated with postmenopausal breast cancer risk. However, it is unclear how and in which life periods PA may be effective to reduce breast cancer risk. Moreover, the evidence is still not judged as ‘convincing’ as there is some heterogeneity among study results. Most studies regarded breast cancer as a single disease, at best separated by menopausal status. Yet, breast cancers are heterogeneous and likely have different etiologies. Therefore, we analyzed the association of PA with different breast cancer subtypes in 3,414 postmenopausal cases and 6,569 controls from a case-control study on breast cancer conducted 2002-2005 in Germany (MARIE study). PA in the age periods 30-49 and 50+ years was assessed, including leisure-time PA (sports, cycling, walking) and non-recreational PA (occupational and household activities). There was a significant protective effect of leisure-time PA for ER+/PR+ carcinomas (adjusted odds ratio = 0.71, 95% confidence interval: 0.60, 0.85; trend P = 0.0001), but no effect for ER-/PR- carcinomas. Moreover, looking at physical activity pattern over time, the effect of PA after menopause on reducing breast cancer risk was more pronounced than the effect of PA before menopause. Overall, effects of PA were independent from adult weight gain, body mass index, and energy intake. These findings suggest that leisure-time PA after menopause may reduce postmenopausal breast cancer risk at least in part via hormonal pathways and not solely by changing body composition. Inactive postmenopausal women should be encouraged to become physically active even later in life. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3402–10)

Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life

BACKGROUNDnExercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer (BC) populations. However, studies investigating exercise during radiotherapy or resistance training are scarce. We conducted a randomized, controlled trial (BEST study) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention.nnnPATIENTS AND METHODSnOne hundred sixty patients with BC stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (RC, 2 times/week). Both interventions were group-based. The primary end point fatigue was assessed with a 20-item multidimensional questionnaire, QoL with EORTC questionnaires. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13.nnnRESULTSnAdherence to the intervention program as well as the completion rate (97%) for the primary outcome variable fatigue was high. In intention-to-treat analyses for the N = 155 patients, significant between-group mean differences (MD) favoring the exercise group (EX) were observed for general fatigue (P = 0.044), especially for the subscale physical fatigue [MD = -0.8; 95% confidence interval -1.5 to -0.2, P = 0.013], but not for affective (P = 0.91) or cognitive fatigue (P = 0.65). For QoL, significantly larger improvements regarding the role function (P = 0.035) and pain (P = 0.040) were noted among exercisers compared with RCs. Future perspective improved significantly stronger in the RC group compared with the EX group (P = 0.047).nnnCONCLUSIONSnThe 12-week resistance training program was a safe, feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy. As exercise was compared with another group-based intervention, results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits, and that the clinically relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher.nnnTRIAL REGISTRATIONnClinicalTrials.gov NCT01468766.

Postmenopausal Sex Hormones in Relation to Body Fat Distribution

Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone‐binding globulin (SHBG). The purpose of this study was to investigate whether a womans body fat distribution shows a BMI‐independent association with these breast cancer‐related biomarkers. Performing cross‐sectional analyses among 1,180 postmenopausal women, we assessed whether associations of surrogates for an abdominal (waist circumference; waist‐to‐hip ratio, WHR) and gluteofemoral (hip circumference) fat distribution with estrone, total and free estradiol, androstenedione, total and free testosterone, and SHBG changed after adjustment for, or stratification by, BMI. All anthropometric measures were positively associated with estrogens and free testosterone, and negatively with SHBG. After adjustment for BMI, associations of free estradiol, free testosterone, and SHBG with both waist circumference and WHR remained significant, but all initially significant associations with hip circumference were abolished. In stratified analyses, waist circumference and WHR correlated with free estradiol, free testosterone, and SHBG in women with a BMI < 30 kg/m2 but not in women with a BMI ≥ 30 kg/m2. The latter suggests that in obese women, a possibly unique effect of abdominal fat on these biomarkers may be masked by the already large amount of overall body fat. On the whole, our results indicate that waist circumference and WHR, but not hip circumference, are associated with SHBG and SHBG‐related sex hormones (free estradiol and free testosterone) independently of BMI.

Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial

Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group‐based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group‐based interventions. One‐hundred‐one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group‐based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20‐item multidimensional questionnaire, QoL with the EORTC QLQ‐C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between‐group pu2009=u20090.098 and 0.052 overall, and pu2009=u20090.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p‐interactionu2009=u20090.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group‐based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy.

Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: The BEST study

BackgroundCancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce.Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood.In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy.Methods/designThe BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed.DiscussionThe BEST study is the first randomized controlled trial comparing progressive resistance training with muscle relaxation training in breast cancer patients during adjuvant radiotherapy. Based on the analysis of physiological, immunological and inflammatory parameters it will contribute to a better understanding of the physiological and psychosocial effects and the biological mechanisms of resistance training. The ultimate goal is the implementation of optimized intervention programs to reduce fatigue, improve quality of life and potentially the prognosis after breast cancer.Trial registrationClinicalTrials.gov NCT01468766

Determinants of long-term fatigue in breast cancer survivors: results of a prospective patient cohort study

Fatigue is among the most distressing symptoms across the breast cancer continuum. However, little is known about the factors contributing to long‐term persisting fatigue. Therefore, we explored determinants of long‐term physical, affective, and cognitive fatigue in a prospective cohort of breast cancer patients.

Association of pre-diagnosis physical activity with recurrence and mortality among women with breast cancer

Evidence is emerging that physical activity (PA) may improve overall survival after breast cancer diagnosis. However, the effect of PA on breast cancer recurrence and on cause‐specific mortality is less investigated. We assessed the association of pre‐diagnosis PA with recurrence, overall and cause‐specific survival in a prospective cohort study in Germany including 3,393 non‐metastatic breast cancer patients aged 50–74 years. Cox proportional hazards models were calculated adjusted for relevant prognostic factors. During a median follow‐up of 5.6 years, 367 patients deceased. Overall mortality was significantly inversely associated with pre‐diagnosis recreational PA. However, this effect was mainly attributed to deaths due to causes other than breast cancer. Multiple fractional polynomial analyses yielded a nonlinear association with markedly increased non‐breast cancer mortality for women who did not engage in any sports or cycling in the years before the breast cancer diagnosis with a hazard ratio (HR, none vs. any) of 1.71, 95% confidence interval (1.16, 2.52). There were no further risk reductions with increasing activity levels. The association with breast cancer‐specific mortality showed a similar dose‐response but was far less pronounced with HR (none vs. any)u2009=u20091.22 (0.91, 1.64). In contrast, regarding cancer recurrence the dose‐response was linear. However, this association was restricted to estrogen/progesterone receptor‐negative (ER−/PR−) cases (pinteractionu2009=u20090.033) with HR (highest vs. no recreational PA)u2009=u20090.53 (0.24, 1.16), ptrendu2009=u20090.0045. Thus, breast cancer patients with a physically inactive lifestyle pre‐diagnosis may decease prematurely irrespective of their cancer prognosis. Higher levels of exercise may reduce the risk of recurrence of ER−/PR− breast tumors.

The Use of Herbal Preparations to Alleviate Climacteric Disorders and Risk of Postmenopausal Breast Cancer in a German Case-Control Study

Background:The use of herbal preparations (HEP) to alleviate climacteric disorders is expected to increase as women seek alternatives to menopausal hormone therapy to avoid the associated breast cancer risk. Data are sparse on the long-term effects of HEP containing phytoestrogens and black cohosh on breast cancer risk. Methods: Within a German case-control study, associations between patterns of HEP use and incident breast cancer were investigated in 10,121 postmenopausal women (3,464 cases, 6,657 controls). Information on HEP use was collected in face-to-face interviews supported by a list of brand names. Multivariate logistic and polytomous regression analyses were done. Findings: Ever use of HEP (9.9%) was inversely associated with invasive breast cancer [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.63-0.87] in a dose-dependent manner (OR, 0.96 per year of use; P = 0.03). Classes of HEP did not differ significantly (Pheterogeneity = 0.81). Risks for invasive ductal (OR, 0.72; 95% CI, 0.60-0.87) and combined lobular/mixed/tubular tumors (OR, 0.76; 95% CI, 0.58-1.01) were similarly reduced by any HEP use but not for in situ carcinomas (1.34; 95% CI, 0.86-2.09). There were no substantial differences in associations of HEP use by estrogen receptor status (ER+ OR, 0.74; 95% CI, 0.62-0.89; ER− OR, 0.68, 95% CI, 0.50-0.93) and progesterone receptor status of the tumor. Interpretation: Our findings support the hypothesis that HEP use protects from invasive breast cancer in postmenopausal women. Among conceivable modes of action, those independent of estrogen receptor–mediated pathways seem to be involved (i.e., cytotoxicity, apoptosis). (Cancer Epidemiol Biomarkers Prev 2009;18(8):2207–13)