Cancer-Related Neuropathic Pain, Chemotherapy-Induced Peripheral Neuropathy and Cognitive Decline in a 5-Year Prospective Study of Patients with Breast Cancer-NEON-BC.

This study aims to estimate the prevalence and to identify the determinants of cancer-related neuropathic pain (CRNP), chemotherapy-induced peripheral neuropathy (CIPN) and cognitive decline among patients with breast cancer over five years after diagnosis. Women with an incident breast cancer (n = 462) and proposed for surgery were recruited at the Portuguese Institute of Oncology-Porto in 2012 and underwent systematic neurological examinations and evaluations with the Montreal Cognitive Assessment (MoCA) before treatment and after one, three, and five years. Multivariate logistic regression was used to assess the determinants of CRNP and CIPN, and multivariate linear regression for the variation in MoCA scores. Prevalence of CRNP and CIPN decreased from the first to the fifth year after diagnosis (CRNP: from 21.1% to 16.2%, p = 0.018; CIPN: from 22.0% to 16.0% among those undergoing chemotherapy, p = 0.007). Cognitive impairment was observed in at least one assessment in 17.7% of the women. Statistically significant associations were observed between: cancer stage III and both CRNP and CIPN; triple negative breast cancer, chemotherapy, axillary node dissection, older age, higher education, and being single and CRNP; taxanes and fruit and vegetable consumption and CIPN. Anxiety, depression and poor sleep quality at baseline were associated with decreases in MoCA values from pre- to post-treatment and with CRNP. Follow-up protocols should consider the persistence of CRNP, CIPN, and cognitive impairment for several years following diagnosis.

Pet ownership during the first 5 years after breast cancer diagnosis in the NEON-BC cohort.

BACKGROUND: Although human-animal interactions (HAI) have been associated with health benefits, they have not been extensively studied among cancer patients nor which factors may influence HAI during cancer survivorship. Therefore, this study aims to describe pet ownership in a breast cancer cohort within 5 years post-diagnosis and to identify associated factors. METHODS: Four hundred sixty-six patients from the NEON-BC cohort were evaluated. Four groups of pet ownership over the 5 years were defined: 'never had', 'stopped having', 'started having' and 'always had'. Multinomial logistic regression was used to quantify the association between the patient characteristics and the groups defined (reference: 'never had'). RESULTS: 51.7% of patients had pets at diagnosis, which increased to 58.4% at 5 years; dogs and cats were the most common. Women presenting depressive symptoms and poor quality of life were more likely to stop having pets. Older and unpartnered women were less likely to start having pets. Those retired, living outside Porto, having diabetes or having owned animals during adulthood were more likely to start having pets. Women with higher education and unpartnered were less likely to always have pets. Those living in larger households, with other adults or having animals throughout life, were more likely to always have pets. Obese women had lower odds of stopping having dogs/cats. Women submitted to neoadjuvant chemotherapy and longer chemotherapy treatments were more likely to stop having dogs/cats. CONCLUSIONS: Pet ownership changed over the 5 years and is influenced by sociodemographic, clinical and treatment characteristics, patient-reported outcomes and past pet ownership, reflecting the importance of HAI during cancer survivorship.

Trajectories of Anxiety and Depression Symptoms over Five Years since Breast Cancer Diagnosis: Results of the NEON-BC Prospective Study.

Anxiety and depression symptoms are frequent among patients with breast cancer (BCa) and may last after initial treatments. We aimed to identify five-year trajectories of anxiety and depression symptoms among women with BCa. Neuro-oncological complications of BCa (NEON-BC) cohort included 506 patients admitted at the Portuguese Institute of Oncology of Porto in 2012, who were evaluated with the Hospital Anxiety and Depression Scale before cancer treatment and after one, three, and five years (7.9% attrition rate). Mixed-effect models were used to model anxiety and depression scores over time and model-based clustering to identify the different trajectories. Three trajectories of anxiety symptoms were identified: (1) high scores at baseline and increasing over time (21.7%); (2) consistently low scores over time (63.6%); (3) mid-range scores at baseline, decreasing over time (14.6%). Three trajectories were identified for depression symptoms: (1) high scores at baseline and increasing over time (21.1%); (2) mid-range scores at baseline, which decreased afterward (58.7%); (3) consistently low levels over time (20.2%). Age, education, baseline, and one-year anxiety/depression status predicted the worst five-year trajectories. These results show that assessing anxiety and depression symptoms before treatment and after one year may contribute to identifying the patients who could benefit the most from psychological support.

Prevalence of Cognitive Impairment before Prostate Cancer Treatment.

Cognitive impairment is common among patients with different types of cancer, even before cancer treatment, but no data were reported among patients with prostate cancer (PCa), who may be at high risk due to advanced age. This study aims to estimate the prevalence of cognitive impairment before PCa treatment. Between February 2018 and April 2021, the NEON-PC cohort recruited 605 patients with PCa proposed for treatment at the Portuguese Institute of Oncology of Porto. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. Participants with a MoCA < 1.5 standard deviations (SD) of age- and education-specific normative values were considered to have probable cognitive impairment (PCI) and were referred for a comprehensive neuropsychological assessment. Data from the population-based cohort EPIPorto (n = 351 men aged ≥40 years, evaluated in 2013−2015) were used for comparison. The prevalence of PCI was 17.4% in EPIPorto and 14.7% in NEON-PC (age- and education-adjusted odds ratio: 0.82, 95%CI: 0.58,1.18). Neuropsychological assessment was performed in 63 patients with PCa: 54.0% had cognitive impairment. These results suggest that the impact of PCa on cognitive performance could be negligible in the short term, contrary to what other studies have reported regarding other types of cancer.

Prevalence and Persistence of Anxiety and Depression over Five Years since Breast Cancer Diagnosis-The NEON-BC Prospective Study.

Anxiety and depression are frequent among patients with breast cancer (BCa). Evidence of the persistence and recovery from these conditions and their determinants is scarce. We describe the occurrence of clinically significant anxiety and depression symptoms and their associated factors among BCa patients. A total of 506 women admitted in 2012 at the Portuguese Institute of Oncology of Porto were evaluated before treatment and after one, three, and five years (7.9% attrition rate). The five-year prevalence of anxiety and/or depression (Hospital Anxiety and Depression Scale, subscores ≥ 11) was 55.4%. The peak prevalence for anxiety was before treatment (38.0%), and after one year for depression (13.1%). One in five patients with anxiety/depression at baseline had persistent anxiety/depression over time, while only 11% and 22% recovered permanently from anxiety and depression, respectively, during the first year. Higher education, higher income, practicing physical activity, and adequate fruit and vegetable intake were protective factors against anxiety and/or depression. Loss of job and income, anxiolytics and antidepressants, cancer-related neuropathic pain, and mastectomy were associated with higher odds of anxiety and/or depression. These results highlight the importance of monitoring anxiety/depression during the first five years after cancer diagnosis and identify factors associated with these conditions.

Interchangeability of two versions of the Montreal Cognitive Assessment for the longitudinal evaluation of patients with breast cancer.

PURPOSE: The cognitive performance of patients with breast cancer (BCa) may be affected by cancer and its treatments. The Montreal Cognitive Assessment (MoCA) is a widely used cognitive impairment screening tool, but practice effects must be considered for longitudinal assessments. Since learning effects could be overcome through the alternate use of two versions of the MoCA, we aimed to explore their interchangeability by comparing their overall, and domain- and task-specific, scores among patients with BCa. METHODS: BCa patients from the NEON-BC cohort were evaluated with the MoCA, version 7.1, after diagnosis and after 1 year. At the 3-year follow-up (n = 422), the 7.1 and 7.3 versions were applied at the beginning and at the end (approximately 1 h later) of this evaluation, respectively. Agreements between versions, regarding total, sub-domain, and task scores, were assessed using Bland-Altman plots and intraclass correlation coefficients (ICC). RESULTS: The mean total scores were not statistically different between versions and the ICC was 0.890. The Bland-Altman limits of agreement were - 3.70 to 3.88. For women with midrange scores, total scores were significantly higher in version 7.1. There were significant differences in the percentage of correct answers in 7 out of 12 tasks, being the highest for the copy of a geometric figure (more than twofold higher with version 7.3). In version 7.1, the language and memory domains presented higher scores and lower visuospatial ability. CONCLUSION: Despite similar overall scores being obtained with the two versions of the MoCA, there were item-specific differences that may compromise their interchangeable use.

Trajectories of cognitive performance over five years in a prospective cohort of patients with breast cancer (NEON-BC).

PURPOSE: To identify trajectories of cognitive performance up to five years since diagnosis and their predictors, in a cohort of patients with breast cancer (BCa). METHODS: A total of 464 women with BCa admitted to the Portuguese Institute of Oncology, Porto, during 2012, were evaluated with the Montreal Cognitive Assessment (MoCA) before any treatment, and after one, three and five years. Probable cognitive impairment (PCI) at baseline was defined based on normative age- and education-specific reference values. Mclust was used to define MoCA trajectories. Receiver Operating Characteristic curves were used to assess the predictive accuracy for cognitive trajectories. RESULTS: Two trajectories were identified, one with higher scores and increasing overtime, and the other, including 25.9% of the participants, showing a continuous decline. To further characterize each trajectory, participants were also classified as scoring above or below the median baseline MoCA scores. This resulted in four groups: 1) highest baseline scores, stable overtime (0.0% with PCI); 2) lowest baseline scores (29.5% with PCI); 3) mid-range scores at baseline, increasing overtime (10.5% with PCI); 4) mid-range scores at baseline, decreasing overtime (0.0% with PCI). Adding the change in MoCA during the first year to baseline variables significantly increased the accuracy to predict the downward trajectory (area under the curve [AUC] = 0.732 vs. AUC = 0.841, P < 0.001). CONCLUSION: Four groups of patients with BCa with different cognitive performance trends were identified. The assessment of cognitive performance before treatments and after one year allows for the identification of patients more likely to have cognitive decline in the long term.

Quality of life trajectories during the first three years after diagnosis of breast cancer: the NEON-BC study.

BACKGROUND: We aimed to identify and characterize quality of life trajectories up to 3 years after breast cancer diagnosis. METHODS: A total of 460 patients were evaluated at baseline (before treatments), and after 1- and 3-years. Patient-reported outcomes, including quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, QLQ-C30), anxiety, depression and sleep quality, were assessed in all evaluations. Model-based clustering was used to identify quality of life trajectories. RESULTS: We identified four trajectories without intersection during 3 years. The two trajectories characterized by better quality of life depicted relatively stable scores; in the other trajectories, quality of life worsened until 1 year, though in one of them the score at 3 years improved. Sociodemographic and clinical characteristics at baseline did not differ between trajectories, except for mastectomy, which was higher in the worst trajectory. Anxiety, depression and poor sleep quality increased from the best to the worst trajectory. CONCLUSIONS: The type of surgery and the variation of other patient-reported outcomes were associated with the course of quality of life over 3 years. More research to understand the heterogeneity of individual trajectories within these major patterns of variation is needed.

Healthcare use and costs in early breast cancer: a patient-level data analysis according to stage and breast cancer subtype.

BACKGROUND: The cost of breast cancer care rises with higher stage at diagnosis; however, there are no real-world data regarding the cost of care according to breast cancer subtypes. This study aimed to estimate direct medical costs for early breast cancer care in the first 3 years after diagnosis according to subtype and stage, using patient-level data. METHODS: Women with newly diagnosed stage I-III breast cancer, admitted in 2012 to a Portuguese cancer centre were prospectively followed within the NEON-BC cohort. The use of health resources was obtained from each patient's clinical and administrative records and costs were computed. Tumours were classified into the classic subtypes (hormone receptor-positive (HR+)/HER2-; HER2-positive (HER2+); triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (luminal A-like; luminal B-like; HER2 enriched; basal like). RESULTS: A total of 703 patients were included: 48.9% had stage I, 35.8% stage II and 15.2% stage III breast cancer; 76.4% had HR+/HER2-, 15.9% HER2+ and 7.7% TNBC. Median cost of care was €9215/patient in stage I, €13 019/patient in stage II and €15 011/patient in stage III and €10 540/patient in HR+/HER2-, €11 224/patient in TNBC and €41 513/patient in HER2+ breast cancer. Systemic therapy accounted for 69.2% of the cost of care among patients with HER2+, 12.0% among HR+/HER2- and 7.5% among TNBC patients. Similar differences were observed across surrogate intrinsic subtypes. CONCLUSIONS: The cost of early breast cancer care was mainly driven by the tumour subtype and, to a lesser extent, by stage. The median cost of care was fourfold higher among patients with HER2+ tumours compared with those with HR+/HER2- and TNBC. These data provide information for the economic evaluation of innovative treatments for early breast cancer and highlight the weight that targeted systemic therapy might have in the overall cost of care among patients with early breast cancer.

Treatment and Other Healthcare Use of Breast Cancer Patients With a Previous Cancer Diagnosis.

BACKGROUND/AIM: To quantify the association between a previous cancer diagnosis and healthcare use among breast cancer (BC) patients, and estimate five-year recurrence-free survival (RFS). PATIENTS AND METHODS: Women with BC were classified according to a previous cancer diagnosis (BC or other). Healthcare use during the first year and five-year RFS were obtained through clinical and administrative records. Adjusted odds ratios and hazard ratios (HR) were estimated. RESULTS: Among 681 BC patients, 21 had a previous BC and 32 a previous non-BC. The latter were less likely to receive anthracycline-based combination chemotherapy. The former had higher odds of mastectomy and genetic testing. Five-year RFS HRs (95% confidence interval) were 2.75 (0.79-9.52) and 0.52 (0.07-3.89) for previous BC and non-BC, respectively. CONCLUSION: Previous cancer was associated with less anthracycline-based combination chemotherapy, and patients were more likely to undergo mastectomy and genetic testing. These findings highlight the need for assessment of previous treatments, personal genetic risk and current BC characteristics.

Changes in employment status up to 5 years after breast cancer diagnosis: A prospective cohort study.

AIM: To assess how sociodemographic, clinical and treatment characteristics impact employment status five-years following a breast cancer diagnosis, and to compare the incidence rate of changes with the general population. METHODS: A total of 462 women with incident breast cancer were evaluated before treatment and three- and five-years later. Adjusted odds ratios (ORs) with 95% confidence intervals (95%CIs) were computed through multinomial logistic regression. Data for comparisons were retrieved from the SHARE Project. Incidence rate ratios (IRRs) with 95%CIs were calculated using Poisson regression. RESULTS: Among the 242 employed women prior to diagnosis, 162 remained employed, 26 became unemployed, 27 entered early retirement, 14 entered normal retirement and 13 were on sick leave at five-years. Unemployment increased with age (≥55 vs < 55 years: OR = 4.49, 95%CI:1.56-12.92; OR = 3.40, 95%CI:1.05-10.97 at three- and five-years, respectively) and decreased with education (>4 vs ≤ 4 years: OR = 0.36, 95%CI:0.13-0.97; OR = 0.27, 95%CI:0.10-0.71 at three- and five-years, respectively). Axillary surgery (unemployment at five-years: OR = 5.13, 95%CI:1.30-20.27), hormonal therapy (unemployment at three-years: OR = 0.28, 95%CI:0.10-0.83) and targeted therapy (sick leave at three-years: OR = 3.79, 95%CI:1.14-12.63) also influenced employment status. Five-years post diagnosis, women with breast cancer had a lower incidence of unemployment (IRR = 0.51, 95%CI:0.30-0.89) than the general population, while, among older women, there was a higher tendency to enter early retirement (IRR = 1.72, 95%CI:0.82-3.61). CONCLUSIONS: Although not all women may want to pursue or continue a professional life following their breast cancer experience; those who do may benefit from social and employer support when returning to work.

Projections in Breast and Lung Cancer Mortality among Women: A Bayesian Analysis of 52 Countries Worldwide.

Among women, lung cancer mortality rates have surpassed those for breast cancer in several countries. This reflects the breast cancer mortality declines due to access to screening and effective treatment alongside the entrance of certain countries in stages of the tobacco epidemic in which smoking becomes more prevalent in women. In this study, we project lung and breast cancer mortality until 2030 in 52 countries. Cancer mortality data were obtained from the WHO Mortality Database. Age-standardized mortality rates (ASMR), per 100,000, were calculated (direct method) for 2008 to 2014 and projected for the years 2015, 2020, 2025, and 2030 using a Bayesian log-linear Poisson model. In 52 countries studied around the world, between 2015 and 2030, the median ASMR are projected to increase for lung cancer, from 11.2 to 16.0, whereas declines are expected for breast cancer, from 16.1 to 14.7. In the same period, the ASMR will decrease in 36 countries for breast cancer and in 15 countries for lung cancer. In half of the countries analyzed, and in nearly three quarters of those classified as high-income countries, the ASMR for lung cancer has already surpassed or will surpass the breast cancer ASMR before 2030. The mortality for lung and breast cancer is higher in high-income countries than in middle-income countries; lung cancer mortality is lower in the latter because the tobacco epidemic is not yet widespread. Due to these observed characteristics of lung cancer, primary prevention should still be a key factor to decrease lung cancer mortality.Significance: The mortality for lung and breast cancer is projected to be higher in high-income countries than in middle-income countries, where lung cancer mortality is expected to surpass breast cancer mortality before 2030. Cancer Res; 78(15); 4436-42. ©2018 AACR.

The use of reperfusion and revascularization procedures in acute coronary syndrome in Portugal: a systematic review.

INTRODUCTION AND OBJECTIVES: Reperfusion and revascularization therapies play an important role in the management of coronary heart disease and have contributed to decreases in case fatality rates. We aimed to describe the use of these therapies for the treatment of acute coronary syndrome (ACS) patients over time in Portugal. METHODS: PubMed was searched in July 2012. The proportion of patients treated with fibrinolysis, primary percutaneous coronary intervention (PCI), any PCI and coronary artery bypass grafting (CABG) was described according to type of ACS: STEMI (≥90% patients with ST-segment elevation or Q-wave myocardial infarction), NSTE-ACS (≥90% patients with non-ST-segment elevation ACS) and mixed ACS (all others). RESULTS: We identified 41 eligible studies, published between 1989 and 2011. Twenty-eight reported on samples considered representative of ACS patients treated in Portugal. The small number of estimates of the use of each treatment in STEMI and NSTE-ACS patients precluded identification of any time trend. In the last 20 years, the proportion of mixed ACS patients treated with fibrinolysis decreased and the use of PCI increased, while the use of CABG did not change. CONCLUSIONS: The general pattern of the use of reperfusion and revascularization is in accordance with that reported in other developed countries, reflecting a favorable trend in the quality of care of ACS patients. The relatively small number of estimates on the same procedure in comparable patients limits the generalizability of the conclusions, and highlights the need for systematic approaches to monitor the use of treatments over time.

[Neuregulin1/ErbB system: importance in the control of cardiovascular function]. / Sistema Neuregulina1/ErbB: importância no controlo da função cardíaca.

The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher risk of cardiomyopathy when co-administered with anthracyclines. Subsequent studies in vitro and in vivo have clarified the effects and the respective signaling pathways associated with the NRG/ErbB system in the adult heart. Some cardiovascular functions of the NRG1/ErbB system have been described at the vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium level (negative inotropic effect) as well as effect on the survival, cell growth and organization of the cardiomyocytes (myofibrillar organization and cell-to-cell contact between cardiomyocytes). Furthermore, the interaction of this system with other neurohumoral mediators has been studied. Thus, there seems to be a physiological role in modulating the sympathovagal balance and an interaction with endothelin-1 signaling. All these effects result from the activation of different intracellular signaling cascades, as a consequence of the binding of NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt, focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial growth factor and NO production by endothelial nitric oxide synthase. Thus, the aim of this paper was to make an up-to-date review of existing information on NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects.