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A Longitudinal Study of Depression, Fatigue, and Sleep Disturbances as a Symptom Cluster in Women With Breast Cancer
GENERAL ISSUES IN BREAST CANCER A Longitudinal Study of Depression, Fatigue, and Sleep Disturbances as a Symptom Cluster in Women With Breast Cancer Ho S-Y, Rohan KJ, Parent J, et al (Univ of Vermont, Burlington; et al) J Pain Symptom Manage 49:707-715, 2015
Context.dDepression, fatigue, and sleep disturbances have been identified as a symptom cluster among breast cancer patients. However, few longitudinal studies have examined the temporal relations between these symptoms surrounding diagnosis and treatment. Objectives.dThe present study investigated the co-occurrence of and interrelations between nonsomatic depressive symptoms, fatigue, and sleep disturbances in breast cancer patients at three time points: before, after, and six to eight months following adjuvant chemotherapy treatment. Methods.dSeparate samples of premenopausal (n ¼ 67) and postmenopausal (n ¼ 67) breast cancer patients completed self-report measures of depression, fatigue, and sleep disturbances at all three time points. Path analysis was used to explore withinand cross-symptom paths across time. Results.dDepression, fatigue, and sleep disturbances were correlated within each time point. Continuity paths, whereby prior levels of symptom severity tended to predict subsequent severity of the same symptom at the subsequent time point, were significant in both samples, except for depression in the premenopausal sample. Instead, significant cross-symptom paths emerged whereby baseline fatigue predicted post-
chemotherapy depression, and postchemotherapy fatigue predicted depression at follow-up in the premenopausal patients. No significant cross-symptom paths emerged for the postmenopausal sample. Conclusion.dFindings supported the notion that depression, fatigue, and sleep disturbances manifest as a symptom cluster. Fatigue may precede nonsomatic symptoms of depression among premenopausal breast cancer patients and represents a potential intervention target. Symptom clusters, defined as 3 (some researchers favor 2) or more symptoms related to each other that may or may not have a common cause, have been a subject of research interest in oncology for more than 15 years.1 Compared with individual symptoms, symptom clusters are thought to have more severe adverse effects on outcomes.2 This may be especially relevant in psycho-oncology, where symptoms of cognitive, mood, and anxiety disorders often overlap with disease and/or treatment-related processesdmaking accurate diagnosis difficultdand where there is intense interest in possible underlying common biological causes (eg, proinflammatory cytokines). In this study, Ho and colleagues used path analysis to assess depressive symptoms, fatigue, and sleep disturbance as a symptom cluster in separate sets of premenopausal (all undergoing chemotherapy) and postmenopausal (undergoing chemotherapy or surgery) women with breast cancer at time points during and up to several months post-treatment. Their data support the construct of the cluster as defined and
show that the severity of symptoms predicted the subsequent severity of the same symptoms over time. In addition, fatigue independently predicted depressive symptoms in premenopausal, but not postmenopausal, women over time. The data in this study met statistical significance for association of the studied symptoms using path analysis; however, as a practical matter, none of this is surprising and would not be expected to change clinical practice. Consider that it is well established that the most severe form of depression, major depressive disorder, is a disease with the same (and additional) emotional and physical symptoms required for diagnosis and also meets the criteria for a symptom cluster. Fatigue of variable severity is almost ubiquitous in cancer patients during and after treatment, and (appropriately noted by the authors) its association with emotional, cognitive, and other constitutional symptoms does not imply causality. As this was not an intervention study, Ho and colleagues overreached in their assertion that their data provide preliminary evidence that targeting fatigue may have a meaningful effect on other related symptoms and “offset” depressive symptoms in women in whom the association exists or would be predicted. While the concept of symptom clusters in oncology is useful and attractive for several reasons, their existence does not simplify care for clinicians. Patients’ ability to cope with symptoms varies (the number or total burden quite possibly contributing); depressive symptoms and depression, for instance, are not the
Breast Diseases: A Year BookÒ Quarterly Vol 26 No 3 2015
203
same thing and should not necessarily be approached in the same way. What is important is that these symptoms are common, though not normal. They should be taken seriously, as they do adversely affect quality of life, ability to tolerate treatment, and possibly disease outcome. Clinicians should be vigilant, screen using recognized assessment instruments, and bring psycho-oncology and supportive/ palliative care resources to bear to
support patients through the disease trajectory and treatment process.3
Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer
mal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. Results.dMean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2$7(2$5) versus 5$9(4$8) per cent respectively; P ¼ 0$006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. Conclusion.dWomen with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. Registration number: ISRCTN84866416 (http://www.isrctn. com).
Bains SK, Peters AM, Zammit C, et al (St George’s, Univ of London, UK; Brighton and Sussex Univ Hosps NHS Trust, UK) Br J Surg 102:534-540, 2015
Background.dBreast cancerrelated lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a ‘stopcock’ effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional ‘global’ lymphatic dysfunction in patients who develop BCRL. Methods.dLower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. 99mTc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnor-
204
A. D. Valentine, MD
References 1. Dodd MJ, Miaskowski C, Paul SM. Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum. 2001;28: 465-470.
Although lymphedema remains one of the most feared sequelae of
Breast Diseases: A Year BookÒ Quarterly Vol 26 No 3 2015
2. Aktas A. Cancer symptom clusters: current concepts and controversies. Curr Opin Support Palliat Care. 2013;7:38-44. 3. Holland J, Jacobsen P, Anderson B, et al. National comprehensive cancer network. NCCN Clinical Practice Guidelines in Oncology. Distress Management. Version 1.2015. http:// www.nccn.org/professionals/ physician_gls/pdf/distress.pdf. Accessed June 4, 2015.
breast cancer treatment, our understanding of the etiology of this ailment is limited. Risk factors such as obesity and axillary lymph node dissection have been shown to confer an increased risk of lymphedema. However, there is relatively meager comprehension of why among breast cancer patients exposed to the same risk factors, some develop lymphedema and some do not. This study by Bains and colleagues sought a greater understanding of lymphatic function in breast cancer patients. The study examined 30 breast cancer patients who had previously undergone axillary lymph node dissection, half of whom had developed upper extremity lymphedema, as well as 24 control patients without a history of either cancer or lymphedema. The authors hypothesized that lymphedema was a global (rather than local) dysfunction of the lymphatic system. They performed lymphoscintigraphy of the lower extremities and found that drainage of the lower extremity lymphatics was diminished among patients with upper extremity lymphedema compared to those without lymphedema. This finding builds on previous work1,2 that has demonstrated lymphatic dysfunction in the contralateral arm of breast
Context.dDepression, fatigue, and sleep disturbances have been identified as a symptom cluster among breast cancer patients. However, few longitudinal studies have examined the temporal relations between these symptoms surrounding diagnosis and treatment. Objectives.dThe present study investigated the co-occurrence of and interrelations between nonsomatic depressive symptoms, fatigue, and sleep disturbances in breast cancer patients at three time points: before, after, and six to eight months following adjuvant chemotherapy treatment. Methods.dSeparate samples of premenopausal (n ¼ 67) and postmenopausal (n ¼ 67) breast cancer patients completed self-report measures of depression, fatigue, and sleep disturbances at all three time points. Path analysis was used to explore withinand cross-symptom paths across time. Results.dDepression, fatigue, and sleep disturbances were correlated within each time point. Continuity paths, whereby prior levels of symptom severity tended to predict subsequent severity of the same symptom at the subsequent time point, were significant in both samples, except for depression in the premenopausal sample. Instead, significant cross-symptom paths emerged whereby baseline fatigue predicted post-
chemotherapy depression, and postchemotherapy fatigue predicted depression at follow-up in the premenopausal patients. No significant cross-symptom paths emerged for the postmenopausal sample. Conclusion.dFindings supported the notion that depression, fatigue, and sleep disturbances manifest as a symptom cluster. Fatigue may precede nonsomatic symptoms of depression among premenopausal breast cancer patients and represents a potential intervention target. Symptom clusters, defined as 3 (some researchers favor 2) or more symptoms related to each other that may or may not have a common cause, have been a subject of research interest in oncology for more than 15 years.1 Compared with individual symptoms, symptom clusters are thought to have more severe adverse effects on outcomes.2 This may be especially relevant in psycho-oncology, where symptoms of cognitive, mood, and anxiety disorders often overlap with disease and/or treatment-related processesdmaking accurate diagnosis difficultdand where there is intense interest in possible underlying common biological causes (eg, proinflammatory cytokines). In this study, Ho and colleagues used path analysis to assess depressive symptoms, fatigue, and sleep disturbance as a symptom cluster in separate sets of premenopausal (all undergoing chemotherapy) and postmenopausal (undergoing chemotherapy or surgery) women with breast cancer at time points during and up to several months post-treatment. Their data support the construct of the cluster as defined and
show that the severity of symptoms predicted the subsequent severity of the same symptoms over time. In addition, fatigue independently predicted depressive symptoms in premenopausal, but not postmenopausal, women over time. The data in this study met statistical significance for association of the studied symptoms using path analysis; however, as a practical matter, none of this is surprising and would not be expected to change clinical practice. Consider that it is well established that the most severe form of depression, major depressive disorder, is a disease with the same (and additional) emotional and physical symptoms required for diagnosis and also meets the criteria for a symptom cluster. Fatigue of variable severity is almost ubiquitous in cancer patients during and after treatment, and (appropriately noted by the authors) its association with emotional, cognitive, and other constitutional symptoms does not imply causality. As this was not an intervention study, Ho and colleagues overreached in their assertion that their data provide preliminary evidence that targeting fatigue may have a meaningful effect on other related symptoms and “offset” depressive symptoms in women in whom the association exists or would be predicted. While the concept of symptom clusters in oncology is useful and attractive for several reasons, their existence does not simplify care for clinicians. Patients’ ability to cope with symptoms varies (the number or total burden quite possibly contributing); depressive symptoms and depression, for instance, are not the
Breast Diseases: A Year BookÒ Quarterly Vol 26 No 3 2015
203
same thing and should not necessarily be approached in the same way. What is important is that these symptoms are common, though not normal. They should be taken seriously, as they do adversely affect quality of life, ability to tolerate treatment, and possibly disease outcome. Clinicians should be vigilant, screen using recognized assessment instruments, and bring psycho-oncology and supportive/ palliative care resources to bear to
support patients through the disease trajectory and treatment process.3
Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer
mal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. Results.dMean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2$7(2$5) versus 5$9(4$8) per cent respectively; P ¼ 0$006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. Conclusion.dWomen with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. Registration number: ISRCTN84866416 (http://www.isrctn. com).
Bains SK, Peters AM, Zammit C, et al (St George’s, Univ of London, UK; Brighton and Sussex Univ Hosps NHS Trust, UK) Br J Surg 102:534-540, 2015
Background.dBreast cancerrelated lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a ‘stopcock’ effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional ‘global’ lymphatic dysfunction in patients who develop BCRL. Methods.dLower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. 99mTc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnor-
204
A. D. Valentine, MD
References 1. Dodd MJ, Miaskowski C, Paul SM. Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum. 2001;28: 465-470.
Although lymphedema remains one of the most feared sequelae of
Breast Diseases: A Year BookÒ Quarterly Vol 26 No 3 2015
2. Aktas A. Cancer symptom clusters: current concepts and controversies. Curr Opin Support Palliat Care. 2013;7:38-44. 3. Holland J, Jacobsen P, Anderson B, et al. National comprehensive cancer network. NCCN Clinical Practice Guidelines in Oncology. Distress Management. Version 1.2015. http:// www.nccn.org/professionals/ physician_gls/pdf/distress.pdf. Accessed June 4, 2015.
breast cancer treatment, our understanding of the etiology of this ailment is limited. Risk factors such as obesity and axillary lymph node dissection have been shown to confer an increased risk of lymphedema. However, there is relatively meager comprehension of why among breast cancer patients exposed to the same risk factors, some develop lymphedema and some do not. This study by Bains and colleagues sought a greater understanding of lymphatic function in breast cancer patients. The study examined 30 breast cancer patients who had previously undergone axillary lymph node dissection, half of whom had developed upper extremity lymphedema, as well as 24 control patients without a history of either cancer or lymphedema. The authors hypothesized that lymphedema was a global (rather than local) dysfunction of the lymphatic system. They performed lymphoscintigraphy of the lower extremities and found that drainage of the lower extremity lymphatics was diminished among patients with upper extremity lymphedema compared to those without lymphedema. This finding builds on previous work1,2 that has demonstrated lymphatic dysfunction in the contralateral arm of breast