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.

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.

O que facilita e dificulta a aprendizagem? a perspetiva de adolescentes / ¿qué facilita y dificulta el aprendizaje? la perspectiva de los adolescentes / What makes learning easier and more difficult? the perspective of teenagers

RESUMO Este estudo qualitativo teve como objetivo analisar as perceções de alunos adolescentes acerca dos aspetos que facilitam e dificultam a sua aprendizagem. O conhecimento das perceções dos alunos sobre a sua aprendizagem permite melhorar a qualidade dos processos de ensino-aprendizagem. A partir de um guião semiestruturado, foram realizados cinco grupos focais, em cinco escolas privadas do Norte de Portugal, tendo participado 32 alunos selecionados aleatoriamente. Os participantes eram alunos do 3º ciclo do Ensino Básico (7º, 8º e 9º anos), com idades compreendidas entre os 12 e os 15 anos. A análise dos dados seguiu um processo semi-indutivo de codificação descritiva. Os resultados realçam o papel fundamental do professor na aprendizagem; a importância da ação vs passividade dos alunos na sala de aula; a relevância da dimensão emocional e relacional para o envolvimento do aluno; e a relevância das estratégias de autorregulação da aprendizagem. Como implicações sugere-se a concretização de ações junto de professores e alunos assente nos dados recolhidos e analisados, que sejam promotoras da metacognição de ambos.

RESUMEN Este estudio cualitativo tuvo como objetivo analizar las percepciones de alumnos adolescentes acerca de los aspectos que facilitan y dificultan su aprendizaje. El conocimiento de las percepciones de los alumnos sobre su aprendizaje permite mejorar la calidad de los procesos de enseñanza-aprendizaje. A partir de un guión semiestructurado, cinco discusiones en grupos focales se llevaron a cabo en cinco escuelas privadas en el Norte de Portugal, que han participado 32 estudiantes seleccionados aleatoriamente. Los participantes eran alumnos del 3º ciclo de la Enseñanza Básica (7º, 8º y 9º años), con edades comprendidas entre los 12 y los 15 años. El análisis de los datos siguió un proceso semi-inductivo de codificación descriptiva. Los resultados subrayan el papel fundamental del profesor para el aprendizaje; la importancia de la acción de los alumnos en el aula versus pasividad; la relevancia de la dimensión emocional y relacional para la participación del alumno y de las estrategias de autorregulación del aprendizaje. Como implicaciones se sugiere la concreción de acciones junto a profesores y alumnos acerca de los datos recogidos y analizados, que sean promotores de la metacognición de ambos.

ABSTRACT This qualitative study aimed to understand the perceptions of adolescent students about what facilitates and hinders their learning. The knowledge of students' perceptions about their learning allows to improve the quality of the learning processes quality. Five focus groups were conducted, with a semi-structured script, in five different private schools from the North of Portugal, having participated in 32 students randomly selected. Participants were students from 7th, 8th and 9th grades, with ages between 12 and 15 years old. The data analysis followed a semi-inductive process and descriptive coding of data. The results highlighted the key role of teachers in students' learning; the importance of students action versus passivity in the classroom; the relevance of emotional and relational dimension to enhance students' engagement, and the relevance of learning self-regulation strategies. As for implications, it is suggested that actions be carried out with teachers and students based on the data collected and analyzed, in order to promote metacognition of both.

A Case of Severe Cholestasis due to Hepatic AL Amyloidosis.

INTRODUCTION: Immunoglobulin light chain-associated amyloidosis results from extracellular tissue deposition of fibril-forming monoclonal immunoglobulin light chains, secreted by a clone of plasma cells. Although the liver is often involved histologically, most cases are clinically asymptomatic, and severe intrahepatic cholestasis as the primary manifestation of the disease is rare. CLINICAL CASE: We report an unusual case of primary amyloidosis in a 71-year-old man, presenting with rapidly progressive cholestasis, associated with hepatomegaly. There are a few reported cases in the literature of cholestasis and acute liver failure as the first manifestations of AL amyloidosis. CONCLUSION: Infiltrative diseases, such as amyloidosis, must be considered when a patient presents with cholestatic hepatitis. A liver biopsy is essential for the diagnosis of amyloidosis when liver test abnormalities dominate the initial clinical presentation. Liver involvement in patients with amyloidosis is often an indicator of poor prognosis.

Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel.

BACKGROUND: Lung (LC), prostate (PCa) and colorectal (CRC) cancers are the most incident in males worldwide. Despite recent advances, optimal population-based cancer screening methods remain an unmet need. Due to its early onset, cancer specificity and accessibility in body fluids, aberrant DNA promoter methylation might be a valuable minimally invasive tool for early cancer detection. Herein, we aimed to develop a minimally invasive methylation-based test for simultaneous early detection of LC, PCa and CRC in males, using liquid biopsies. RESULTS: Circulating cell-free DNA was extracted from 102 LC, 121 PCa and 100 CRC patients and 136 asymptomatic donors' plasma samples. Sodium-bisulfite modification and whole-genome amplification was performed. Promoter methylation levels of APCme, FOXA1me, GSTP1me, HOXD3me, RARß2me, RASSF1Ame, SEPT9me and SOX17me were assessed by multiplex quantitative methylation-specific PCR. SEPT9me and SOX17me were the only biomarkers shared by all three cancer types, although they detected CRC with limited sensitivity. A "PanCancer" panel (FOXA1me, RARß2me and RASSF1Ame) detected LC and PCa with 64% sensitivity and 70% specificity, complemented with "CancerType" panel (GSTP1me and SOX17me) which discriminated between LC and PCa with 93% specificity, but with modest sensitivity. Moreover, a HOXD3me and RASSF1Ame panel discriminated small cell lung carcinoma from non-small cell lung carcinoma with 75% sensitivity, 88% specificity, 6.5 LR+ and 0.28 LR-. An APCme and RASSF1Ame panel independently predicted disease-specific mortality in LC patients. CONCLUSIONS: We concluded that a DNA methylation-based test in liquid biopsies might enable minimally invasive screening of LC and PCa, improving patient compliance and reducing healthcare costs. Moreover, it might assist in LC subtyping and prognostication.

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.

Acute airway obstruction due to benign multinodular goitre.

Benign multinodular goitre is a common illness. When accompanied by obstructive symptoms, such as dyspnoea, it carries an indication for surgery. Benign multinodular goitres rarely cause acute airway obstruction. We report the case of a 88-year-old woman who presented with acute shortness of breath and stridor. A chest CT revealed marked enlargement of the thyroid gland, with an extensive intrathoracic component. She was proposed for total thyroidectomy. Her intraoperative course was unremarkable, but the patient passed away in postoperative period from ventricular fibrillation. Recognition of these cases is important, as they constitute a preventable cause of mortality if timely diagnosed and treated.

Factors associated with time to breast cancer diagnosis and treatment in unscreened women in Portugal.

Delays in detection, diagnosis and treatment may lead to poorer prognosis in women with breast cancer. We quantified time intervals from first detection (FD) to diagnosis (D) and first treatment (FT) and identified associated factors. We studied 282 patients diagnosed with breast cancer during 2012 at the Breast Clinic of the Portuguese Institute of Oncology in Porto, Portugal using face-to-face interview and medical records. Associations of sociodemographic and clinical characteristics with time intervals was computed using adjusted percentage differences (adjPD) after logarithmic transformation, odds ratios (adjOR) for comparing the highest and lowest thirds of the distribution and 95 percent confidence intervals (CI) for both measures, using linear and logistic regression, respectively. The median times between FD and D and FT were 31 and 44 days, respectively. Significantly longer periods between FD and D were found in symptomatic women (adjPD = 99.5, 95 percent CI: 37.1, 190.0; adjOR = 3.16, 95 percent CI: 1.57, 6.33). More advanced stage was associated with shorter intervals between D and FT (adjPD = -33.8, 95 percent CI: -44.2, -21.5; adjOR = 0.14, 95 percent CI: 0.05, 0.34). Although some differences according to clinical characteristics were observed, they did not seem to translate into inequities in access to public healthcare in this group of women.

Changes in health behaviours and body mass index after a breast cancer diagnosis: results from a prospective cohort study.

The aim of the study was to describe changes in health behaviours and BMI after breast cancer diagnosis, depicting the potential influence of sociodemographic, clinical and psychological characteristics. A total of 428 breast cancer patients were prospectively followed for 3 years, since diagnosis. At the end of follow-up, women were classified regarding their adherence to recommendations for cancer prevention, prediagnosis and after 3 years, including not smoking, alcohol consumption up to one drink per day, intake of at least five portions per day of fruits and/or vegetables, physical activity and body mass index (BMI) less than 25.0 kg/m. To quantify associations between patients' characteristics and changes in adherence to each recommendation, age, education and cancer stage-adjusted odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Among women adhering to each recommendation before diagnosis, 54.1% reduced their physical activity, 32.4% became overweight or obese and 6.1% reduced fruits and/or vegetables intake, but there were virtually no changes in alcohol consumption or smoking. Older and more educated participants were more likely to reduce their physical activity (OR=4.71, 95% CI: 1.17-18.99; OR=11.53, 95% CI: 2.20-60.53, respectively). Among participants not following each recommendation before diagnosis, 29.1% stopped smoking, 24.6% reduced alcohol consumption, 9.9% became physically active, 7.8% increased fruits and/or vegetables intake and 3.3% reduced their BMI to less than 25.0 kg/m. Older women were less likely to become physically active (OR=0.32, 95% CI: 0.14-0.75). Breast cancer patients showed some positive changes in their health behaviours after diagnosis. However, there is a large margin for improvement, which highlights the importance of health promotion interventions in this context.

Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women.

BACKGROUND: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. METHODS: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RARß2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers' diagnostic performance was also evaluated. RESULTS: A "PanCancer" panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a "CancerType" panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. CONCLUSIONS: CcfDNA's methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects' triage, increasing compliance and cost-effectiveness.

Neuropathic Pain After Breast Cancer Treatment: Characterization and Risk Factors.

CONTEXT: Neuropathic pain (NP) may be an important contributor to the morbidity burden of breast cancer. OBJECTIVES: We aimed to quantify the incidence of NP in the first year after diagnosis of breast cancer and to identify its main determinants. METHODS: We performed a prospective cohort study including 506 patients with incident breast cancer, recruited at the Portuguese Institute of Oncology of Porto, and followed for one year; patients with incident NP were additionally evaluated when this condition was diagnosed and after six months, to identify chronic NP. RESULTS: During the first year, 156 patients were diagnosed with NP (30.8%, 95% CI 27.0-35.0). Anxiety (relative risk [RR] 1.50; 95% CI 1.06-2.13), arm symptoms (RR 1.44; 95% CI 1.02-2.05), cancer Stage III/IV (RR 2.47; 95% CI 1.66-3.66), breast-conserving surgery with axillary lymph node dissection (RR 3.13; 95% CI 1.51-6.48), mastectomy with axillary lymph node dissection (RR 2.52; 95% CI 1.25-5.11), and damaging of the intercostobrachial nerve (RR 2.05; 95% CI 1.25-3.37) were predictors of a higher risk of NP. A total of 97 patients (62.2%, 95% CI 54.4-69.4) diagnosed with NP remained symptomatic after six months. CONCLUSION: NP and chronic NP were frequent in this population, being associated with anxiety and arm symptoms before breast cancer treatments and type of surgical management. These results highlight the need for monitoring the occurrence of this neurologic side effect of treatments and to develop strategies for reducing the morbidity burden of breast cancer.

A rare missense variant in RET exon 8 in a Portuguese family with atypical multiple endocrine neoplasia type 2A.

BACKGROUND AND OBJECTIVE: Multiple Endocrine Neoplasia type 2 (MEN2) is a rare genetic disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism. MEN2 is an autosomal dominant syndrome caused by mutations in the RET proto-oncogene. In the vast majority of patients, the mutations are localized in exons 10, 11 and 13-15 of the RET gene. Rare variants located in exon 8 were recently identified but their clinical significance remains unclear. DESIGN AND METHODS: We studied two sisters presenting with pheochromocytoma as the first tumor. One of the sisters was diagnosed with a right pheochromocytoma at the age of 44 and at age 53 she developed an invasive left pheochromocytoma with no other endocrine neoplasia. The other sister was diagnosed with a left pheochromocytoma at age 50 and at age 64 she had a right phemochromocytoma and MTC. Neither of the two sisters presented evidence of primary hyperparathyroidism. Mutations of the RET proto-oncogene were investigated by DNA sequencing. RESULTS: We detected a germline missense variant in RET exon 8 (p.Cys531Arg) in both sisters. The p.Cys531Arg variant was not present in a third 50-year-old sister who has remained to date clinically unaffected. CONCLUSION: This is the first case showing the p.Cys531Arg variant in RET exon 8 co-segregating with family members affected by a syndrome reminiscent of MEN2A. Our results suggest that this variant has a specific genotype-phenotype correlation as it is associated with the development of pheochromocytoma before the onset of MTC.

Chemotherapy-induced peripheral neuropathy after neoadjuvant or adjuvant treatment of breast cancer: a prospective cohort study.

PURPOSE: The purposes of this study were to estimate the incidence of chemotherapy-induced peripheral neuropathy (CIPN) and to identify its main determinants and impact in patient-reported outcomes. METHODS: We performed a prospective cohort study including 296 patients with incident breast cancer submitted to chemotherapy, followed for 1 year. Patients with incident CIPN were reevaluated 6 months after this diagnosis. Relative risks (RR) with 95 % confidence intervals (95 % CI) were computed to quantify the relation between different clinical characteristics and the occurrence of CIPN, using Poisson regression. The variation of patient-reported outcomes between baseline and 1-year follow-up assessments was compared between patients with and without CIPN. RESULTS: The cumulative incidence of CIPN in the first year after diagnosis was 28.7 % (95 % CI 23.8-34.1), and more than 80 % of the patients were still symptomatic after 6 months. Among the latter, there was a significant decrease in the median total neuropathy score, clinical version (7 versus 4) between the two periods. In multivariable analysis, the risk of CIPN was higher for treatment with docetaxel (cumulative doses ≤300 mg/m(2), RR = 6.96, 95 % CI 2.53-19.10; >300 mg/m(2), RR = 13.32; 95 % CI 4.11-43.14). Alcohol consumption and diabetes were not significantly associated with CIPN. There were no significant differences in the variation of patient-reported outcomes between the baseline and 1-year follow-up evaluations. CONCLUSIONS: CIPN was frequent in this contemporary cohort of early-stage breast cancer patients and was strongly associated with docetaxel-based regimens. Symptoms persisted for at least 6 months in most patients, but severity was low and CIPN had no impact on patient-reported outcomes.

Neurological complications of breast cancer: A prospective cohort study.

OBJECTIVES: Neurological complications secondary to breast cancer treatment may be an important contributor to these patients morbidity. We aimed to quantify the incidence of neurological complications of breast cancer treatment during the first year after diagnosis. MATERIALS AND METHODS: We performed a prospective cohort study with 506 patients recruited at the Portuguese Institute of Oncology of Porto, among those newly diagnosed. Participants underwent a neurological examination before treatment, after surgery, after chemotherapy (whenever applicable) and at one year after enrollment. The Montreal Cognitive Assessment was used to assess cognitive function, at baseline and at one year. We computed one-year cumulative incidence estimates and the corresponding 95% confidence intervals (95%CI) for each of the neurological complications. RESULTS: Just over half of women had breast cancer stage 0 or I. A total of 6.9% were submitted to neoadjuvant chemotherapy but most of them completed adjuvant treatment - endocrine therapy, radiotherapy or chemotherapy (83.9%, 73.0% and 52.5%, respectively). The cumulative incidence of at least one oncological-related neurological complication during the first year after diagnosis was 48.4% (95%CI: 44.1-52.8); the most frequent were neuropathic pain (30.8%, 95%CI: 27.0-35.0), chemotherapy-induced peripheral neuropathy (16.8%, 95%CI: 13.8-20.3), phantom breast pain/syndrome (16.6%, 95%CI: 13.6-20.1) and cognitive decline (8.1%, 95%CI: 5.8-11.1). CONCLUSIONS: Neurological complications were a frequent side-effect of breast cancer management in the first year after diagnosis, especially neuropathic pain and chemotherapy-induced peripheral neuropathy. Accurate diagnosis and treatment of these complications are important to minimize the burden associated with breast cancer treatment in breast cancer survivors.