Fatigue among Long-Term Breast Cancer Survivors: A Controlled Cross-Sectional Study.

BACKGROUND: Fatigue is the most common and persistent symptom among women in the first five years after a breast cancer diagnosis. However, long-term prevalence of fatigue, among breast cancer survivors, needs further investigation. AIM: To compare fatigue experienced by long-term breast cancer survivors with that in a reference population and to evaluate the determinants of that fatigue. DESIGN AND SETTING: A cross-sectional cohort study of 350 breast cancer survivors ≥5 years after diagnosis and a reference population of 350 women matched by age and general practitioner. METHOD: Fatigue was measured using the Multidimensional Fatigue Inventory (MFI-20), and a sum score of >60 (multidimensional fatigue) was the primary outcome. Logistic regression was applied to compare the prevalence of multidimensional fatigue between the survivor and reference populations, adjusted for body mass index (BMI) and for cardiovascular and psychological variables. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated. Logistic regression was applied to evaluate the determinants of multidimensional fatigue among the survivors. RESULTS: Breast cancer survivors (median 10 years after diagnosis), more often experienced multidimensional fatigue than the reference population (26.6% versus 15.4%; OR, 2.0 [95%CI, 1.4-2.9]), even after adjusting for confounders. The odds of multidimensional fatigue were also higher among survivors with symptoms of depression (32.2% versus 2.7%; OR, 17.0 [95%CI, 7.1-40.5]) or anxiety (41.9% versus 10.1%; OR, 6.4 [95%CI, 3.6-11.4]). CONCLUSION: One in four breast cancer survivors experience multidimensional fatigue and fatigue occurs more frequently than in women of the same age and general practitioner. This fatigue appears to be associated with symptoms of depression and anxiety.

Long-term survivors of early breast cancer treated with chemotherapy are characterized by a pro-inflammatory biomarker profile compared to matched controls.

BACKGROUND: Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls. METHODS AND RESULTS: In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. CONCLUSION: Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro-inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors.

A systematic review on the prevalence of symptoms of depression, anxiety and distress in long-term cancer survivors: Implications for primary care.

INTRODUCTION: Symptoms of depression, anxiety and distress are common in the first years after a cancer diagnosis, but little is known about the prevalence of these symptoms at the long term. The aim of this review was to describe the prevalence of symptoms of depression, anxiety and distress in long-term cancer survivors, five or more years after diagnosis, and to provide implications for primary care. METHODS: We performed a systematic literature search in the PubMed, PsycINFO and CINAHL databases. Studies were eligible when reporting on the prevalence of symptoms of depression, anxiety and/or distress in long-term cancer survivors (≥5 years after diagnosis), treated with curative intent. RESULTS: A total of 20 studies were included. The reported prevalence of depressive symptoms (N = 18) varied from 5.4% to 49.0% (pooled prevalence: 21.0%). For anxiety (N = 7), the prevalence ranged from 3.4% to 43.0% (pooled prevalence: 21.0%). For distress (N = 4), the prevalence ranged from 4.3% to 11.6% (pooled prevalence: 7.0%). CONCLUSION: Prevalences of symptoms of depression, anxiety and distress among long-term survivors of cancer do not fundamentally differ from the general population. This is reassuring for primary care physicians, as they frequently act as the primary physician for long-term survivors whose follow-up schedules in the hospital have been completed.

Cardiac Function After Radiation Therapy for Breast Cancer.

PURPOSE: The main purpose of this study was to test the hypothesis that incidental cardiac irradiation is associated with changes in cardiac function in breast cancer (BC) survivors treated with radiation therapy (RT). METHODS AND MATERIALS: We conducted a cross-sectional study consisting of 109 BC survivors treated with RT between 2005 and 2011. The endpoint was cardiac function, assessed by echocardiography. Systolic function was assessed with the left ventricular ejection fraction (LVEF) (n = 107) and the global longitudinal strain (GLS) of the left ventricle (LV) (n = 52). LV diastolic dysfunction (n = 109) was defined by e' at the lateral and septal region, which represents the relaxation velocity of the myocardium. The individual calculated RT dose parameters of the LV and coronary arteries were collected from 3-dimensional computed tomography-based planning data. Univariable and multivariable analysis using forward selection was performed to identify the best predictors of cardiac function. Robustness of selection was assessed using bootstrapping. The resulting multivariable linear regression model was presented for the endpoints of systolic and diastolic function. RESULTS: The median time between BC diagnosis and echocardiography was 7 years. No relation between RT dose parameters and LVEF was found. In the multivariable analysis for the endpoint GLS of the LV, the maximum dose to the left main coronary artery was most often selected across bootstrap samples. For decreased diastolic function, the most often selected model across bootstrap samples included age at time of BC diagnosis and hypertension at baseline. Cardiac dose-volume histogram parameters were less frequently selected for this endpoint. CONCLUSIONS: This study shows an association between individual cardiac dose distributions and GLS of the LV after RT for BC. No relation between RT dose parameters and LVEF was found. Diastolic function was most associated with age and hypertension at time of BC diagnosis. Further research is needed to make definitive conclusions.

Long-term outcome of cardiac function in a population-based cohort of breast cancer survivors: A cross-sectional study.

BACKGROUND: Chemotherapy and radiotherapy for breast cancer may lead to cardiac dysfunction, but the prevalence of long-term echocardiographic evidence of cardiac dysfunction is unknown among survivors. METHODS: In a cross-sectional study in primary care, we included 350 women who survived breast cancer for at least 5 years after diagnosis (treated with chemotherapy and/or radiotherapy) and 350 matched women (age and primary care physician). The primary outcome was cardiac dysfunction, defined as a left ventricular ejection fraction (LVEF) < 54% and an age-corrected decreased left ventricular (LV) diastolic function. Secondary outcomes included serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, newly diagnosed cardiovascular diseases and cardiovascular medication. RESULTS: The median age at diagnosis was 63 (interquartile range (IQR) 57-68) years for the breast cancer survivors. Median follow-up after diagnosis was 10 (IQR 7-14) years. LVEF < 54% was present in 52 (15.3%) survivors and 24 (7%) controls (OR 2.4, 95%CI 1.4-4.0), but there was no significant increased prevalence of either LVEF < 50% or LV diastolic dysfunction. Serum NT-proBNP levels were increased, cardiovascular disease was more frequently diagnosed and cardiovascular medication use was more frequent among survivors compared with controls. These associations remained after adjustment for relevant covariates at diagnosis and at follow-up. CONCLUSIONS: In the long term, breast cancer survivors are at increased risk of mild LV systolic dysfunction, increased NT-proBNP levels, and cardiovascular disease compared with matched controls, even after adjustment for cardiovascular risk factors. Previous breast cancer treatment with chemotherapy, radiotherapy or both should be considered when assessing a patient's cardiovascular risk profile.

A single pre-operative antibiotic dose is as effective as continued antibiotic prophylaxis in implant-based breast reconstruction: A matched cohort study.

PURPOSE: Infections following implant-based breast reconstruction can lead to devastating consequences. There is currently no consensus on the need for post-operative antibiotics in preventing immediate infection. This study compared two different methods of infection prevention in this group of patients. METHOD: A retrospective matched cohort study was performed on consecutive women undergoing implant-based breast reconstruction at University Health Network, Toronto (November 2008-December 2012). All patients received a single pre-operative intravenous antibiotic dose. Group A received minimal interventions and Group B underwent maximal prophylactic measures. Patient (age, smoking, diabetes, co-morbidities), oncologic and procedural variables (timing and laterality) were collected. Univariate and multivariate logistic regression were performed to compare outcomes between the two groups. RESULTS: Two hundred and eight patients underwent 647 implant procedures. After matching the two treatment groups by BMI, 94 patients in each treatment group yielding a total of 605 implant procedures were selected for analysis. The two groups were comparable in terms of patient and disease variables. Post-operative wound infection was similar in Group A (n = 11, 12%) compared with Group B (n = 9, 10%; p = 0.8). Univariate analysis revealed only pre-operative radiotherapy to be associated with the development of infection (0.004). Controlling for the effect of radiotherapy, multivariate analysis demonstrated that there was no statistically significant difference between the two methods for infection prevention. CONCLUSIONS: Our findings suggest that a single pre-operative dose of intravenous antibiotics is equally as effective as continued antibiotic prophylaxis in preventing immediate infection in patients undergoing implant-based breast reconstructions.

Systematic Review: Aesthetic Assessment of Breast Reconstruction Outcomes by Healthcare Professionals.

BACKGROUND: Achieving an aesthetic outcome following postmastectomy breast reconstruction is both an important goal for the patient and plastic surgeon. However, there is currently an absence of a widely accepted, standardized, and validated professional aesthetic assessment scale following postmastectomy breast reconstruction. METHODS: A systematic review was performed to identify all articles that provided professional assessment of the aesthetic outcome following postmastectomy, implant- or autologous tissue-based breast reconstruction. A modified version of the Scientific Advisory Committee's Medical Outcomes Trust (MOT) criteria was used to evaluate all professional aesthetic assessment scales identified by our systematic review. The criteria included conceptual framework formation, reliability, validity, responsiveness, interpretability, burden, and correlation with patient-reported outcomes. RESULTS: A total of 120 articles were identified: 52 described autologous breast reconstruction, 37 implant-based reconstruction, and 29 both. Of the 12 different professional aesthetic assessment scales that exist in the literature, the most commonly used scale was the four-point professional aesthetic assessment scale. The highest score on the modified MOT criteria was assigned to the ten-point professional aesthetic assessment scale. However, this scale has limited clinical usefulness due to its poor responsiveness to change, lack of interpretability, and wide range of intra- and inter-rater agreements (Veiga et al. in Ann Plast Surg 48(5):515-520, 2002). CONCLUSIONS: A "gold standard" professional aesthetic assessment scale needs to be developed to enhance the comparability of breast reconstruction results across techniques, surgeons, and studies to aid with the selection of procedures that produce the best aesthetic results from both the perspectives of the surgeon and patients.

Cardiac output measurement by bioimpedance and noninvasive pulse contour analysis compared with the continuous pulmonary artery thermodilution technique.

OBJECTIVE: The aim of the present study was to compare 2 noninvasive cardiac output measurement methods with the continuous cardiac output thermodilution (CCO-TD) method. DESIGN: A single-center prospective design. SETTING: A university hospital. PARTICIPANTS: Fifty-three consecutive patients scheduled for elective, non-emergent cardiac surgery. INTERVENTIONS: With each participant the cardiac output was measured using 3 methods: CCO-TD, the Endotracheal Cardiac Output Monitor (ECOM), and the Nexfin monitor. MEASUREMENTS AND MAIN RESULTS: Measurements were performed simultaneously at 7 time points: After induction, before cardiopulmonary bypass, after cardiopulmonary bypass, after protamine, after arrival in the intensive care unit, and before extubation on postoperative day 1. Statistical analysis was performed using Pearson's correlation, Bland-Altman, percent error, and polar plots. Compared to CCO-TD, ECOM showed significant correlation of R0.619 with a bias of -0.13 L/min (95% confidence interval -2.19-1.93 L/min), a percent error of 40%, and trending ability of 87% and 97% within 0.5 L/min and 1.0 L/min, respectively. The Nexfin monitor showed significant correlation of R0.535 with a bias of-0.35 L/min (95% confidence interval-3.36-2.66 L/min), a percent error of 58% and trending ability of 84% and 97% were within 0.5 L/min and 1.0 L/min limits of agreement. CONCLUSIONS: Neither the ECOM nor the Nexfin had the ability to replace the thermodilution-based continuous cardiac output monitor. The ECOM did not have acceptable accuracy or trending ability and only could be utilized for intubated patients. The Nexfin lacked reliability and trending ability. Also, the Nexfin did not provide consistent results.

Using propensity score analysis to compare major complications between DIEP and free muscle-sparing TRAM flap breast reconstructions.

BACKGROUND: Previous studies comparing muscle-sparing transverse rectus abdominis myocutaneous (TRAM) versus deep inferior epigastric artery perforator (DIEP) free flaps have not considered procedure selection bias. Propensity score analysis provides a statistical approach to consider preoperative factors in flap selection, and was used to compare major complications (breast and abdominal) between these microsurgical breast reconstruction (free muscle-sparing TRAM versus DIEP). METHODS: This study evaluated major breast and abdominal complications in 292 consecutive patients (428 free abdominal flaps). Propensity scores were calculated for patient differences affecting flap selection (DIEP versus free muscle-sparing TRAM). Multivariate logistic models using selected covariates separately analyzed breast and abdominal complications between flap methods. RESULTS: There were 83 major complications (28 percent): breast, 20 percent; abdomen, 8 percent. Using propensity scores, the adjusted odds of abdominal complications were significantly higher in free muscle-sparing TRAM than in DIEP flaps (OR, 2.73; 95 percent CI, 1.01 to 7.07). With prior chemotherapy, body mass index significantly increased abdominal complications (OR, 1.16; 95 percent CI, 1.01 to 1.34). Using propensity scores, there was no significant association between reconstruction method and breast complications; diabetics had significantly increased breast complications (OR, 4.19; 95 percent CI, 1.14 to 15.98). Previous abdominal operations (OR, 1.77; 95 percent CI, 0.96 to 3.30) and immediate reconstruction (OR, 1.86; 95 percent CI, 0.94 to 3.71) approached significance. CONCLUSIONS: Propensity score analysis indicated significantly higher abdominal complications in free muscle-sparing TRAM compared with DIEP flaps. This study highlights the importance of separately evaluating recipient breast and donor abdominal complications and use of propensity scores to minimize procedure selection bias. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.