Longitudinal Relationships Among Breast Cancer Survivors Essay

Longitudinal Relationships Among Breast Cancer Survivors Essay

Hello students: In previous weeks we have been reviewing the prevalence, mortality and morbidity associated with breast cancer. This is a topic of extreme public and personal interest. Primary care providers deal with the diagnosis, and the screening of breast cancer on a daily basis. Therefore, in this discussion we will discuss about the importance of understanding the advantages and limitations of its screening Longitudinal Relationships Among Breast Cancer Survivors Essay

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Breast cancer screening is often done through physical exam and also biopsy, but there is some dilemma on cases of over-diagnosis of ductal carcinoma in situ (DCIS) where evidence shows there is now clear evidence that between 10 and 50% of invasive cancers detected and treated radically as a result of screening would never threaten life (Hughes et al., 2014). The benefit of screening healthy populations by mammography was questionable and had little, if any, effect on mortality. But these concerns have not been shared with women invited to participate in screening.

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The main benefit of mammography screening is reduction of breast-cancer related death. Overdiagnosis of breast cancer is the main harm of mammography screening. Based on recent estimates from the United States, the relative amount of overdiagnosis (including ductal carcinoma in situ and invasive cancer) is 31%. This results in 15 women overdiagnosed for every 1,000 women invited to biennial mammography screening for 20 years from age 50 (Brandãoa, Tavares, Schulz & Matosa, 2016).

References

Brandãoa, T., Tavares, R., Schulz, M. S., & Matosa, P. M. (2016). Measuring emotion regulation and emotional expression in breast cancer patients: A systematic review. Clinical Psychology Review, 43, 114-117. doi:10.1016/j.cpr.2015.10.002

Hughes, S., Jaremka, L. M., Alfano, C. M., Glaser, R., Povoski, S. P., Lipari, A. M., . . . Kiecolt-Glaser, J. K. (2014). Social support predicts inflammation, pain, and depressive symptoms: Longitudinal relationships among breast cancer survivors. Psychoneuroendocrinology, 42, 38-44. doi:10.1016/j.psyneuen.2013.12.016  Longitudinal Relationships Among Breast Cancer Survivors Essay

Breast cancer is one of the most common cancers worldwide, with almost 80% of patients expecting long-term disease-free survival. As cure rates have substantially improved, there is now an increased awareness of long-term side effects of cancer treatment [1,2,3]. Cancer-related fatigue and cognitive complaints are common symptoms after breast cancer diagnosis and treatment. Both of these symptoms can persist for years after the end of primary treatment and result in substantial adverse physical, psychosocial, and socio-economic consequences [4,5,6,7,8,9,10].
This review presents an update of the state of the art regarding long-term fatigue and cognitive disorders in patients with early breast cancer, describing prevalence, impact, pathophysiology, and risk factors, and focuses on available interventions. We performed a narrative review of studies published up until September 2019. We restricted our search to papers in the English language, and included observational studies, randomized controlled trials, as well as meta-analyses and systematic reviews.
2. Long-Term Cancer-Related Fatigue in Breast Cancer Survivors: Prevalence, Trajectory, and Impact
2.1. Assessment and Prevalence
Cancer-related fatigue is an extremely prevalent long-term side effect among breast cancer survivors [11], defined as “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer and/or cancer treatment that is not proportional to recent activity and interferes with usual functioning” [12]. Cancer-related fatigue can have distinct physical, cognitive, and emotional dimensions, and seems to be more severe, persistent, and debilitating than normal fatigue. Several studies have suggested that the intensity and duration of fatigue experienced by cancer patients and survivors is significantly greater than that of individuals without a history of cancer [13,14].
Because fatigue is a subjective experience, the gold standard to evaluate cancer-related fatigue is self-reporting. A practical way of evaluating fatigue is to ask patients to evaluate their fatigue using a scale ranging from 0–10, which classifies fatigue as mild if patients score 1–3, moderate if 4–6, and severe if 7–10. In addition, cancer-related fatigue can be evaluated by a number of validated questionnaires that vary from single-item to multi-dimensional instruments, which can characterize different aspects of fatigue, including severity, duration, interference, and dimensions. Some of the validated instruments to assess cancer-related fatigue are listed in Table 1 [5,6,8]. Of note, the great heterogeneity that exists in instruments to evaluate fatigue is often reported as a major limitation in the available literature.Longitudinal Relationships Among Breast Cancer Survivors Essay
Table 1. Validated instruments to assess self-reported fatigue [5,6,8].
Table
Overall, during the phase of active treatment, the vast majority of patients experience some fatigue, with 30–60% categorizing their fatigue as moderate or severe, depending on patient population, patterns of treatment, and instrument of evaluation. Although fatigue typically improves after completion of primary treatment for breast cancer (surgery, radiation, and/or chemotherapy), around 30% of patients continue to experience severe fatigue in the year after treatment, and 20% of patients still report severe fatigue at 10 years post-treatment [5,6,8]. Recently, investigators from the Mind-Body Study characterized five longitudinal trajectories of fatigue after breast cancer treatment over time up to 6 years after treatment among 191 breast cancer patients [15]. The identified groups included: (1) High fatigue (11%), characterized by persistently elevated fatigue; (2) recovery (28%), characterized by initially high but then decreasing fatigue; (3) late (17%), characterized by initially low but gradually increasing fatigue; (4) low (34%), characterized by initially low and gradually decreasing fatigue; and (5) very low (10%), characterized by persistently stable and low fatigue.
2.2. Impact of Cancer-Related Fatigue after Breast Cancer
Data suggest that fatigue can affect patients’ social and work lives (e.g., a small minority of patients will be so debilitated by fatigue that they will be unable to work or regain their premorbid level of health) [11]. Fatigue can substantially impact breast cancer survivors’ ability to respond to work demands, in particular in the case of heavy workload or work-related stress. In addition, fatigue may have substantial negative consequences on quality of life and other daily activities. Cancer-related fatigue is often associated with severe emotional and role dysfunction and with a lack of life meaning [6,7,16]. Reports show that patients consider fatigue as a highly distressing symptom, which is often being referred to as more difficult to cope with than vomiting or pain [17]. Nevertheless, despite the prevalence and impact of this symptom, data also suggest that fatigue is highly underreported by patients and remains an often unaddressed issue by oncology providers.
2.3. Risk Factors and Mechanisms of Long-Term Cancer-Related Fatigue after Treatments for Breast Cancer
Fatigue is a complex and multidimensional symptom. A number of studies have investigated and proposed a variety of risk factors and mechanisms of onset for long-term cancer-related fatigue [8,18].Longitudinal Relationships Among Breast Cancer Survivors Essay
2.3.1. Risk Factors of Cancer-Related Fatigue
Demographic and contextual factors such as young age, being single, having a low income, as well as medical and psychosocial factors, including multiple comorbidities, physical inactivity, elevated body mass index, pre-treatment fatigue, depression, early stress, sleep disturbance, dysfunctional coping, and loneliness, have all been associated with increased risk of fatigue [18]. In this setting, pre-treatment fatigue has been identified as the most consistent predictor of post-treatment fatigue [11]. In addition, tumor and treatment factors can also impact risk of cancer-related fatigue. Patients with higher cancer stage are at increased risk of fatigue, as well as those treated with combination modalities that include surgery and radiotherapy with or without hormonotherapy. On the contrary, patients treated only with local strategies such as surgery with or without radiotherapy are at lower risk of severe fatigue [5,6,8]. More recently, some studies also identified genetic risk factors that were linked to increased risk of developing cancer-related fatigue. Most of such studies focused on genes associated with inflammation using a candidate-gene approach. Among these, polymorphisms in TNFa, IL6, and IL1-b were associated with fatigue after breast cancer treatment completion. However, these results were not consistently replicated across studies. These polymorphisms have been associated with fatigue also in non-cancer populations, suggesting that they may play a role in the biology underlying fatigue in a more generalizable fashion [19,20].
2.3.2. Mechanisms of Cancer-Related Fatigue
Several mechanisms have been proposed to be linked with cancer-related fatigue. These include, among others, inflammation, hypothalamic pituitary adrenal (HPA) dysfunction, five hydroxyl tryptophan (5-HT) dysregulation, alterations in the autonomic nervous system, alterations in adenosine triphosphate and muscle metabolism, changes in leukocyte subsets, reactivation of latent herpes viruses, anemia, and down-regulation of genes with response elements for the glucocorticoid receptor [21,22,23,24,25]. The lack of longitudinal studies in this setting makes it difficult to interpret whether or not all of the cited biological changes are only driven by cancer and cancer treatment or might also be present before cancer diagnosis.Longitudinal Relationships Among Breast Cancer Survivors Essay

The most commonly explored biological and mechanistic model for cancer-related fatigue involves inflammation and associated neurologic activation. Several studies have documented increased inflammation markers post breast cancer treatment, including elevation of IL-1β, TNF-α, IL-6, soluble TNF receptor type II (sTNF-RII), IL-1 receptor antagonist (IL-1RA), soluble IL-6 receptor (sIL-6R), and C-reactive protein (CRP), with the hypothesis that peripheral inflammatory cytokines may promote signals to the central nervous system that generate symptoms of fatigue [11,26,27,28]. This is consistent with studies performed among otherwise healthy individuals where sub-clinical levels of inflammatory markers are associated with the development of fatigue [11,29,30,31]. These data can intersect with evidence highlighting the relation of fatigue and alterations of the HPA axis and autonomous nervous system. Indeed, both of these systems have important anti-inflammatory effects since they interfere with cytokine production, or, such as in the case of the HPA axis, via glucocorticoid production or decreased sensitivity of glucocorticoid receptor [11,21,27,32,33,34,35]. Another biological process that may influence fatigue includes alterations of the immune system, which can also be linked with increased inflammation [11,21,27,32,33,34].
3. Interventions to Reduce Cancer-Related Fatigue
Several types of interventions have proved to be beneficial in reducing cancer-related fatigue among survivors of breast cancer, although no clear superiority of one over the other has been demonstrated, and standards are lacking to select the most appropriate intervention for individual patients. Most of these interventions are thought to be effective because they reduce inflammation or disrupt pro-inflammatory circuits [11]. Leading cancer societies, including the National Comprehensive Cancer Network (NCCN), the Oncology Nursing Society (ONS), and the American Society of Clinical Oncology (ASCO), have released several recommendations about interventions that can be offered to patients to reduce cancer-related fatigue. Most of these recommendations are based on studies that largely included breast cancer survivors.
Assessment and correction of treatable contributing factors, including nutrition status (e.g., vitamin status, weight/caloric intake changes, and fluid electrolyte imbalances), are strongly encouraged before considering interventions to reduce fatigue.

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A summary of the proposed interventions for cancer-related fatigue is presented in Table 2.Longitudinal Relationships Among Breast Cancer Survivors Essay
Table 2. Interventions to reduce fatigue among survivors of breast cancer post-treatment.
Table
3.1. Counseling and Education on Cancer-Related Fatigue
In a Cochrane review of randomized trials among cancer patients, educational interventions reduced cancer-related fatigue and its interference with daily life [36]. Therefore, in general, all patients should be educated on cancer-related fatigue (e.g., how it differs from normal fatigue, what are the contributing factors, and how to self-monitor fatigue levels, and how to manage cancer-related fatigue). This is particularly relevant for patients that receive treatments that have been linked with increased risk of cancer-related fatigue, including radiation and chemotherapy. Cancer survivors should always be made aware of providers and facilities they can refer to in order to engage in programs that may help reduce cancer-related fatigue, and this includes distant-based alternatives. Indeed, studies have also shown that counseling can also be effectively delivered remotely via tele-health/internet to patients that are not in the active phase of treatment [37].
3.2. Physical Activity Interventions
Among non-pharmacologic interventions, the strongest and most consistent evidence supports the effectiveness and safety of physical activity interventions in reducing cancer-related fatigue. A large number of studies have evaluated the impact of exercise on fatigue in the active treatment or immediate post-treatment settings, with fewer data available on longer-term cancer-related fatigue. A meta-analysis of 27 exercise intervention trials showed that exercise training among patients with various types of cancer led to a significant reduction in fatigue. Exercise significantly reduced cancer-related fatigue with a mean effect size of 0.32 (95% Confidence Interval [CI] 0.21–0.43) during cancer treatment and 0.38 (95% CI 0.21–0.54) following treatment completion. In the post-treatment setting, longer time between treatment completion and exercise intervention initiation and shorter exercise program length were linked to larger improvements in fatigue score [38]. In another meta-analysis of 72 studies among patients with either solid or hematological or mixed malignancies, exercise reduced cancer-related fatigue compared to control, with a moderate effect (standardized mean difference (SMD), −0.45; 95% CI −0.57 to −0.32) [39]. Finally, a Cochrane meta-analysis conducted including 56 randomized trials, 36 of which enrolled patients in the phase of active cancer treatment, demonstrated that there was both a decrease in fatigue from baseline to 12 weeks after baseline and better fatigue scores at 12 weeks after baseline, favoring patients in the exercise intervention arms (SMD, −0.38; 95% CI −0.57 to −0.18 and SMD −0.73; 95% CI −1.14 to −0.31, respectively) [40].Longitudinal Relationships Among Breast Cancer Survivors Essay
Based on these data, the National Comprehensive Cancer Network (NCCN) diffused guidelines supporting physical activity intervention as a Category 1 recommendation for the treatment of cancer-related fatigue, particularly among patients who have completed treatment [12]. Although there is still no evidence to recommend a specific amount of physical activity, all patients are encouraged to engage in at least moderate levels of physical activity after cancer treatment to reduce cancer-related fatigue, as reported in specific guidelines published by ASCO. A minimum of 150 minutes of moderate aerobic exercise per week is sufficient to meet the threshold of the recommended level, and this may include whatever form of aerobic training (e.g., fast walking, cycling, or swimming) in addition to 2–3 sessions of strength training (e.g., including weight lifting), unless specific contraindications exist [41].
Nevertheless, exercise interventions to reduce cancer-related fatigue should be tailored to the individual patient, based on factors including age, gender, and baseline level of physical fitness. Specifically, the choice of the most appropriate physical activity intervention to offer should account for patients’ medical history and comorbidities (including neuropathy, cardiomyopathy, or other long-term effects of therapy), as well as for physical limitations, risk of injury, and other safety concerns, particularly in the case of structural bone problems or blood test abnormalities such as moderate-to-severe anemia or thrombocytopenia [12]. However, several exercise programs exist that are suitable and considered safe for most cancer survivors, particularly those programs that are walking-based.Longitudinal Relationships Among Breast Cancer Survivors Essay
Some evidence has demonstrated that yoga interventions are able to reduce fatigue during cancer treatment. The majority of tested interventions were conducted among women with breast cancer undergoing chemotherapy. For example, a small randomized clinical trial included 60 patients with breast cancer during active adjuvant chemotherapy, and showed that 8 weeks of Anusara yoga sessions twice per week improved fatigue [42]. Nevertheless, evidence on the relationship between engaging in yoga practices and reduction in cancer-related fatigue is not always consistent. A larger trial of 352 women with early-stage breast cancer receiving chemotherapy failed to demonstrate that participation in a Tibetan yoga program during active chemotherapy and over the following six months significantly reduces cancer-related fatigue compared to a stretching program or usual care; despite this, the yoga program was associated with better sleep outcomes in exploratory analyses, and an amelioration of such sleep parameters may in turn translate into improved cancer-related fatigue Longitudinal Relationships Among Breast Cancer Survivors Essay

This study describes how cancer survivors’ information needs about recurrence, late effects, and family risks of cancer evolve over the course of their survivorship period. Three annual surveys were conducted from 2006 to 2008 in a cohort of Pennsylvania cancer survivors diagnosed with colon, breast, or prostate cancer in 2005 (Round 1 N=2013, Round 2 N=1293, Round 3 N = 1,128). Outcomes were information seeking about five survivorship topics. Key predictors were survey round, cancer diagnosis, and the interaction between these variables. Mixed effects logistic regression analyses were performed to predict information seeking about each topic, adjusting for demographic variables, clinical characteristics, and clustering of repeated observations within individuals. Information seeking about reducing risks of cancer recurrence was the most frequently reported topic across survivors and over time. Breast cancer survivors were more likely to seek about survivorship topics at Round 1 compared with other survivors. In general, information seeking declined over time, but cancer-specific patterns emerged: the decline was sharpest for breast cancer survivors whereas in later years female colon cancer survivors actually sought more information (about how to reduce the risk of family members getting colon cancer or a different cancer). Cancer survivors’ information needs varied over time depending on the topic, and these trends differed by cancer type. Clinicians may need to intervene at distinct points during the survivorship period with information to address concerns about cancer recurrence, late effects, and family members’ risks. Copyright © 2015, American Association for Cancer Research. Longitudinal Relationships Among Breast Cancer Survivors Essay