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OBJECTIVES: To describe the Quality of Life (QOL) of breast-cancer patients diagnosed with COVID-19 and analyse its evolution, compare the QOL of these patients according to the COVID-19 wave in which they were diagnosed, and examine the clinical and demographic determinants of QOL. METHODS: A total of 260 patients with breast cancer (90.8% I-III stages) and COVID-19 (85% light/moderate) were included (February-September 2021) in this study. Most patients were receiving anticancer treatment (mainly hormonotherapy). Patients were grouped according to the date of COVID-19 diagnosis: first wave (March-May 2020, 85 patients), second wave (June-December 2020, 107 patients) and third wave (January-September 2021, 68 patients). Quality of Life was assessed 10 months, 7 months, and 2 weeks after these dates, respectively. Patients completed QLQ-C30, QLQ-BR45, and Oslo COVID-19 QLQ-PW80 twice over four months. Patients ≥65 also completed QLQ-ELD14. The QOL of each group and changes in QOL for the whole sample were compared (non-parametric tests). Multivariate logistic regression identified patient characteristics related to (1) low global QOL and (2) changes in Global QOL between assessments. RESULTS: Moderate limitations (>30 points) appeared in the first assessment in Global QOL, sexual scales, three QLQ-ELD14 scales, and 13 symptoms and emotional COVID-19 areas. Differences between the COVID-19 groups appeared in two QLQ-C30 areas and four QLQ-BR45 areas. Quality of Life improvements between assessments appeared in six QLQ-C30, four QLQ-BR45 and 18 COVID-19 questionnaire areas. The best multivariate model to explain global QOL combined emotional functioning, fatigue, endocrine treatment, gastrointestinal symptoms, and targeted therapy (R2 = 0.393). The best model to explain changes in global QOL combined physical and emotional functioning, malaise, and sore eyes (R2 = 0.575). CONCLUSIONS: Patients with breast cancer and COVID-19 adapted well to illness. The few differences between wave-based groups (differences in follow-up notwithstanding) may have arisen because the second and third waves saw fewer COVID restrictions, more positive COVID information, and more vaccinated patients.
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Neoplasias de la Mama , COVID-19 , Humanos , Femenino , Calidad de Vida/psicología , COVID-19/epidemiología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Encuestas y Cuestionarios , Modelos LogísticosRESUMEN
PURPOSE: General population normative data for the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire facilitates interpretation of data assessed from cancer patients. This study aims to present normative data of the general Spanish population. METHODS/PATIENTS: Data were obtained from a prior larger study collecting EORTC QLQ-C30 norm data across 15 countries. Data were stratified by sex and age groups (18-39, 40-49, 50-59, 60-69 and > 70 years). Sex and age distribution were weighted according to population distribution statistics. Sex- and age-specific normative values were analysed separately, as were participants with versus those without health conditions. Multiple linear regression was used to estimate the association of each of the EORTC QLQ-C30 scales with the determinants age, sex, sex-by-age interaction term, and health condition. RESULTS: In total, 1,165 Spanish individuals participated in the study. Differences were found by sex and age. The largest sex-related differences were seen in fatigue, emotional functioning, and global QOL (Quality of Life), favouring men. The largest age differences were seen in emotional functioning, insomnia, and pain, with middle-aged groups having the worst scores. Those > 60 years old scored better than those < 60 years old on all scales except for physical functioning. Participants with no health conditions scored better in all QLQ-C30 domains. CONCLUSIONS: The present study highlights differences in HRQOL between specific sex/age strata and especially between people with and without a health condition in the general Spanish population. These factors must be considered when comparing general population HRQOL data with that of cancer patients.
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Estado de Salud , Encuestas Epidemiológicas/estadística & datos numéricos , Neoplasias/terapia , Calidad de Vida/psicología , Encuestas y Cuestionarios/normas , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Análisis de Datos , Fatiga/epidemiología , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Distribución por Sexo , Factores Socioeconómicos , España/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: Although new therapies against metastatic cancer have been developed in recent decades, chemotherapy is still an important treatment option. Prolonged treatment and side-effects are often discouraging for patients, and in many cases, therapy is only palliative, not curative. This study explores patient preference for oral or intravenous (IV) chemotherapy in the treatment of metastatic breast or lung cancer. METHODS: It is a descriptive, open label, multicentre, nation-wide study, in which a 16-item questionnaire consisting of single-choice questions scored on a 5-point Likert scale was administered to patients in a single visit, and another 11-item questionnaire was self-administered by the patient's oncologist. RESULTS: A total of 131 breast and lung cancer specialists at 64 hospitals enrolled 412 patients (lung cancer = 161; breast cancer = 251). To be eligible, patients must have already received IV therapy and at least 2 cycles of oral chemotherapy. Most (77%) patients expressed preference for oral therapy. Most considered their daily life was less disrupted with tablets (70.4%), had no trouble swallowing them (86.9%), and were not concerned about forgetting to take them (56.8%). Half (56.3%) were worried about problems related to drug infusion with IV therapy, 61.7% were concerned about nurses failing to find a suitable vein, and 63.1% were dissatisfied with hospital waiting times. A uniform response was obtained from both samples of patients. CONCLUSION: Convenience, ease of administration, fewer side effects and better quality of life tilt the balance towards oral drug administration.
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Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Prioridad del Paciente , Administración Oral , Neoplasias de la Mama/psicología , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/psicología , Masculino , Dolor Asociado a Procedimientos Médicos , Calidad de Vida , España , Encuestas y Cuestionarios , ComprimidosRESUMEN
AIM OF THE STUDY: Quality of life (QL) is important in premenopausal long-term breast cancer survivors. In this study we assessed QL and factors associated with future perspective and global QL in premenopausal early-stage long-term breast cancer survivors from Spain. MATERIAL AND METHODS: 243 premenopausal stage I-IIIA relapse-free breast cancer patients who had received surgery 5-20 years previously completed EORTC QLQ-C30 and QLQ-BR23 questionnaires once during follow-up. Univariate and multivariate logistic regression analyses were performed. RESULTS: QL mean scores were high in most areas (> 80 in functioning; < 20 in symptoms). The main factors for future perspective were emotional and social functioning, fatigue, breast symptom, and body image. The main factors for global QL were fatigue, pain and physical functioning, and emotional and social functioning. The best logistic model to explain future perspective associated high emotional and social functioning and low breast symptoms with a lower risk of low future perspective (R(2) = 0.56). Higher scores in physical and emotional functioning and lower scores in fatigue were associated with a lower risk of low global QL (R(2) = 0.50). CONCLUSIONS: Psychological, social, and physical factors were found to be possible determinants of global QL and future perspective. QL in premenopausal early-stage long-term breast cancer survivors may benefit from multidisciplinary treatment.
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OBJECTIVE: This study evaluates satisfaction with care (SC) in cancer patients treated at a Spanish day hospital to identify SC determinants and assess the relationship between SC and quality of life. METHODS: One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Cancer Outpatient Satisfaction with Care questionnaire for chemotherapy (OUT-PATSAT35 CT), the Oberst patients' perception of care quality and satisfaction scales, and an item on intention to recommend the hospital. Frequencies in the SC instruments, Spearman correlations between each scale of the OUT-PATSAT35 CT and overall satisfaction and between the subscales of OUT-PATSAT35 CT and of QLQ-C30 were calculated, and the determinants of patients' SC were calculated through multivariate regression models. RESULTS: Satisfaction with care was high: mean scores were >70 in all OUT-PATSAT35 CT areas except doctor availability and environment. These scores were in line with the other SC instruments. Correlation with overall satisfaction was high and statistically significant (p < 0.01) for all subscales, especially for the nurses domain, which also had higher SC scores. Correlations between the EORTC QLQ-C30 and the OUT-PATSAT35 CT were low (≤ 0.35). Younger patients and those with breast cancer showed significantly lower satisfaction in most subscales. Unmarried patients and patients that had undergone surgery reported lower satisfaction only in specific subscales. CONCLUSIONS: Satisfaction with care among cancer patients treated at the day hospital is high. Nurses play a key and successful role. Age and tumour location revealed stronger relationships with SC. Correlations between SC and quality of life indicate that these concepts are complementary.
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Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pacientes Ambulatorios/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida/psicología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/psicología , Pacientes Ambulatorios/psicología , Relaciones Profesional-Paciente , Psicometría , Calidad de la Atención de Salud , Reproducibilidad de los Resultados , Factores Sexuales , Factores Socioeconómicos , España , Encuestas y CuestionariosRESUMEN
OBJECTIVE: In this article, the quality of life (QOL) of Spanish postmenopausal early-stage breast cancer patients who have finished endocrine therapy (ET), QOL changes after endocrine therapy cessation, and the differences between two endocrine therapy modalities (tamoxifen or aromatase inhibitor [AI]) are studied. More QOL information after endocrine therapy cessation is needed. METHODS: A prospective cohort study was performed. Participating in the study were 158 postmenopausal patients who had received tamoxifen or AI for 5 years. In some cases, endocrine therapy may have changed during those 5 years.Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR45 questionnaires at baseline, after 6 months, and after 1 year of follow-up. Patients older than 65 years also completed the QLQ-ELD14. Linear mixed-effect models were used to evaluate longitudinal changes in QOL and differences in QOL between endocrine therapy modalities. RESULTS: QOL scores for the whole sample throughout follow-up were high (>80/100 points) in most QOL areas. Moderate limitations (>30 points) occurred in the QLQ-BR45 in sexual functioning and sexual enjoyment, future perspective, and joint symptoms. Moderate limitations also occurred in the QLQ-ELD14 in worries about others, maintaining purpose, joint stiffness, future worries, and family support. In those who had finished endocrine therapy, pain was reduced in all three assessments conducted during the 1-year follow-up period in both groups. Tamoxifen patients showed better QOL in functioning (role functioning, global QOL, financial impact), symptoms (pain), and emotional areas (future perspective and worries about others) than AI patients but worse QOL in skin mucosis symptoms. CONCLUSIONS: The results of this study show that postmenopausal early-stage breast cancer patients adapted well to their disease and endocrine therapy treatment. QOL improvements in the 1-year follow-up period appeared in one key area: pain. Differences between endocrine therapy modalities suggested QOL was better in the tamoxifen group than in the AI group.
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Neoplasias de la Mama , Tamoxifeno , Femenino , Humanos , Neoplasias de la Mama/terapia , Dolor , Posmenopausia , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Tamoxifeno/uso terapéuticoRESUMEN
PURPOSE: The OUT-PATSAT35 CT questionnaire evaluates satisfaction with care expressed by cancer outpatients receiving chemotherapy. This study assesses the psychometric properties of the OUT-PATSAT35 CT when applied to a sample of Spanish patients. METHODS: One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30, the OUT-PATSAT35 CT, the Oberst patients' perception of care quality and satisfaction scales (OS) and the item on intention to recommend the hospital (IR). Psychometric evaluation of the structure, reliability and validity of the questionnaire was conducted. RESULTS: Multitrait scaling analysis showed that 32 of 34 item-scale correlation coefficients met the standards for convergent validity and that many of them met the standards for discriminant validity. Cronbach's coefficients were good (0.78-0.97) for all scales except doctor availability and environment. Correlations between the QLQ-C30 and the OUT-PATSAT35 CT were low (≤0.40). Correlations between IR and the OUT-PATSAT35 CT were moderate, and correlations between this questionnaire and the OS were fairly low. Areas whose contents were more related had higher correlation coefficients (>0.50) and vice versa (<0.1). Male patients, elderly patients, those with higher education levels, those with higher scores in four OS and patients who had not received surgery showed higher satisfaction with care in several OUT-PATSAT35 CT areas. CONCLUSIONS: The OUT-PATSAT35 CT is a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the validation study conducted by the authors of the questionnaire and with the validation study for Spain of the OUT-PATSAT35 RT.
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Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pacientes Ambulatorios/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Pacientes Ambulatorios/psicología , Relaciones Profesional-Paciente , Psicometría/instrumentación , Reproducibilidad de los Resultados , Factores Sexuales , España , Encuestas y CuestionariosRESUMEN
This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2-C5). Tumour proliferation and hypoxic status were evaluated using 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)- and 18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.
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BACKGROUND AND OBJECTIVES: Quality of life (QoL) is a key outcome for elderly cancer patients. The EORTC has developed QLQ-ELD14, a questionnaire that assesses important age-specific issues for older patients with cancer. This study aims to validate QLQ-ELD14 for use with elderly Spanish breast cancer patients. MATERIALS AND METHODS: A consecutive sample of breast cancer patients with localized disease (age ≥65) who had received surgery ≥5 years earlier, were disease-free, and may have received adjuvant treatments was included. Patients completed the QLQ-ELD14, QLQ-C30 and QLQ-BR23 questionnaires. A subsample of patients completed QLQ-ELD14 six months later. Psychometric evaluation of the structure, reliability and validity of QLQ-ELD14 was conducted. RESULTS: 87 patients completed the first assessment and 30 the second. Multitrait scaling analysis showed that all items except two met the standards for convergent and divergent validity. Cronbach's coefficient met the 0.7 alpha criterion on all scales except worries about others. Areas of QLQ-ELD14 and QLQ-C30 whose contents are conceptually related correlated substantially (Spearman's Rho >0.40). Conversely, areas of QLQ-ELD14 that had less in common with those of QLQ-C30 and QLQ-BR23 had low correlations (Spearman's Rho <0.1). Differences in QLQ-ELD14 were found in groups based on age, disease duration, living arrangement, presence of limiting comorbidity, and level of performance status. Patients had a higher level of worries at the second assessment. CONCLUSIONS: QLQ-ELD14 is a reliable and valid instrument when applied to a sample of Spanish patients. Our results are in line with those of other validation studies.
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Neoplasias de la Mama/terapia , Encuestas Epidemiológicas/instrumentación , Calidad de Vida , Factores de Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Rendimiento Físico Funcional , Psicometría , Reproducibilidad de los Resultados , Características de la Residencia , España , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
BACKGROUND: Eribulin has efficacy in patients with progression after ≥ 1 chemotherapeutic regimen for metastatic breast cancer (MBC). A short disease-free interval (DFI) and previous use of taxanes in the neoadjuvant or adjuvant setting have been associated with worse outcomes for patients receiving first-line chemotherapy for HER2-negative MBC. The aim of the present trial was to evaluate the efficacy and safety of eribulin as first-line therapy for patients with HER2-negative MBC with these poor prognostic factors. PATIENTS AND METHODS: Eribulin monotherapy was administered until disease progression or unacceptable toxicity. The principal selection criteria were HER2 negativity without previous chemotherapy for MBC, the previous use of taxanes for early-stage breast cancer, and a DFI of < 36 months (subsequently amended to 48 months). The primary endpoint was the investigator-assessed time to progression. The secondary endpoints included overall survival, progression-free survival, objective response rate, clinical benefit rate, duration of response, and toxicity profile. A total of 53 patients were enrolled and received ≥ 1 dose of eribulin. RESULTS: The median patient age was 47 years (range, 23-82.8 years). The median DFI was 15.7 months (range, 0.1-46.4 months). The median investigator-assessed time to progression was 4.1 months (range, 0.2-27.8 months; 95% confidence interval, 3.2-6.2 months). The objective response and clinical benefit rate was 20.8% and 26.4%, respectively. All-grade and grade 3/4 adverse events developed in 96.2% and 69.8% of patients, respectively. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and anemia. CONCLUSION: Eribulin is effective and safe as first-line therapy for aggressive taxane-pretreated HER2-negative MBC.
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Antimitóticos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Furanos/uso terapéutico , Cetonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antimitóticos/efectos adversos , Antineoplásicos/efectos adversos , Hidrocarburos Aromáticos con Puentes/farmacología , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Furanos/efectos adversos , Humanos , Cetonas/efectos adversos , Persona de Mediana Edad , Metástasis de la Neoplasia , Receptor ErbB-2/metabolismo , Taxoides/farmacología , Taxoides/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1-34) ranged from 77.8-99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences.
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INTRODUCTION: There are few studies on the effect on quality of life (QL) of cancer-related illness and treatment in elderly patients. The aim of this work was to evaluate prospectively QL in a sample of elderly patients with stages I.III breast cancer who started radiotherapy treatment and compare their QL with that of a sample of younger patients. MATERIALS AND METHODS: Forty-eight patients, > or = 65 years of age completed the European Organization for Research and Treatment of Cancer (EORTC) QL questionnaires QLQ-C30 and QLQ-BR23, and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) daily activities scale three times throughout treatment and follow-up periods. Clinical and demographic data were also recorded. Fifty patients ages 40-64 years with the same disease stage and treatment modality had previously completed the QL questionnaires. QL scores, changes in them among the three assessments, differences between groups based on clinical factors, and differences between the two samples were calculated. RESULTS: QL scoring was good and stable (>70/100 points) in most areas, in line with clinical data. Light and moderate limitations occurred in global QL and some emotional, sexual, and treatment-related areas. Moderate decreases (10-20) appeared in some toxicity-related areas, which recovered during the follow-up period. Breast-conservation and sentinel-node patients presented higher scores in emotional areas. There were few QL differences among agebased samples. CONCLUSIONS: QL and clinical data indicate radiotherapy was well tolerated. Age should not be the only factor evaluated when deciding upon treatment for breast cancer patients.
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Neoplasias de la Mama/psicología , Neoplasias de la Mama/radioterapia , Calidad de Vida/psicología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
PURPOSE: This paper studies the Quality of Life (QL) of elderly early-stage breast cancer survivors. The aims are to compare the QL scores of these patients after follow-up with their scores before the start of radiotherapy (RT) and compare QL among different axillary treatment groups. METHODS: Of 173 patients over 65 who began treatment and completed the EORTC QLQ-C30 and QLQ-BR23 and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) before RT, 138 also completed these questionnaires three years after RT. Longitudinal changes in QL were assessed for the whole sample using linear mixed-effect models. Also assessed were differences in QL scores between axillary treatment groups (axillary node dissection ALND, sentinel lymph node biopsy SLNB, and no surgery) at the end of the follow-up (Anova or Kruskal-Wallis) and differences in the evolution of QL from baseline among these groups (linear regression models). RESULTS: QL scores in the follow-up were high (>70/100 points) in most QL areas, with moderate limitations (>30) in sexual functioning and enjoyment. Five areas (pain, nausea/vomiting, financial impact, breast symptoms and IDDD) improved significantly (<6 points) in the follow-up. The ALND group scored less for the future perspective item (15-20 points) in the follow-up than the other two axillary treatment groups. No differences between the pre-treatment and follow up assessments regarding treatment were found among the axillary treatment groups. CONCLUSIONS: Our results suggest that early-stage breast cancer patients adapted well both to their disease and treatments over the follow-up period and to the administration of RT. There were few QL differences between the axillary treatment groups.
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Neoplasias de la Mama/radioterapia , Supervivientes de Cáncer/estadística & datos numéricos , Calidad de Vida , Anciano , Axila/patología , Axila/cirugía , Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático/estadística & datos numéricos , Metástasis Linfática , Mastectomía/estadística & datos numéricos , Persona de Mediana Edad , España , Encuestas y CuestionariosRESUMEN
The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry. A panel of five BC cell lines was treated with two epigenetic drugs, and restoration of CHL1 expression was observed, indicating in vitro dynamic epigenetic regulation. CHL1 was silenced by shRNA in immortalized but non-neoplastic mammary cells, and enhanced cell proliferation and migration, but not invasion, were found by real-time cell analysis. The prognostic value of CHL1 hypermethylation was assessed by the log-rank test and fitted in a Cox regression model. Importantly, CHL1 hypermethylation was very significantly associated with shorter progression-free survival in our BC patient series, independent of age and stage (p = 0.001). In conclusion, our results indicate that CHL1 is downregulated by hypermethylation and that this epigenetic alteration is an independent prognostic factor in BC.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Moléculas de Adhesión Celular/genética , Metilación de ADN , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Moléculas de Adhesión Celular/biosíntesis , Movimiento Celular/genética , Proliferación Celular/genética , Islas de CpG/genética , Supervivencia sin Enfermedad , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Interferencia de ARN , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ADN/estadística & datos numéricosRESUMEN
PURPOSE: This paper studies the Quality of Life (QL) of Spanish advanced non-small-cell lung cancer (NSCLC) patients receiving platinum-doublet chemotherapy, compares our results with those from studies from other cultural areas, and identifies factors associated with global QL and survival prognostic variables. METHODS: EORTC QLQ-C30 and QLQ-LC13 questionnaires were completed three times by 39 patients along treatment and follow-up. Univariate and multivariate logistic regression analyses were performed to study global QL determinants (≤50 points considered low global-QL score). Analyses of prognostic variables for death were performed (Cox proportional hazards models). RESULTS: QL mean scores in the whole sample were moderately high, with limitations (>30) in physical, role, social functioning, emotional areas, fatigue, pain, neuropathy and global QL. Differences with studies from other cultural areas were mainly found in the lower score for dyspnoea (≥15 points). There were no significant differences in QL scores between the first and second assessments. In six areas, the third assessment was lower than the first and second: fatigue, hair loss (>20 points); physical, social functioning, neuropathy (10-20 points); emotional functioning (5-10 points). The best model to explain the chances of low QL includes, as explanatory variables, high emotional functioning as protective factor and fatigue as risk factor (R(2) = 0.70). Eight QL areas (four pain-related) and performance status showed a statistically significant association with survival. CONCLUSION: Patients adapted well to their disease and treatments. Platinum-doublet can be administered in advanced NSCLC patients. Our QL data are in line with those from other cultural areas.
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PURPOSE: There is a debate on the role of adjuvant Radiotherapy (RT) in elderly breast cancer patients. The aim is to study Quality of Life (QL) throughout the treatment and follow-up periods in early stages breast cancer patients who have started radiotherapy, and to compare the QL of axillary surgery groups. METHODS: 173 patients, ≥65 years completed the EORTC QLQ-C30 and QLQ-BR23, and the Interview for Deterioration in Daily Living Activities in Dementia(IDDD) questionnaires three times throughout treatment and follow-up periods. Linear mixed effect models were used to evaluate longitudinal changes in QL, and whether these changes differed among axillary surgery groups. RESULTS: QL scores were high (>70/100 points) in most QL areas, with moderate limitations (>30) in sexual functioning and enjoyment, future perspective and global QL. In six areas there was a decline at the RT sessions end, that after 6 weeks was recovered. For three areas, there was an improvement in the follow-up measurement compared to the previous assessments. Changes in seven areas were <5 points. Axillary node dissection patients had a body image decrease (6 points) in the follow up period. The lymphadenectomy group had more fatigue (10 points, p = 0.078) than the other two axillary surgery groups. CONCLUSIONS: Results orientate towards good patients' adaptation to their disease and treatments, and to administering RT in early stages breast cancer patients. QL differences between the axillary surgery groups and in their evolutions were few but have appeared in key QL areas.
Asunto(s)
Neoplasias de la Mama/radioterapia , Calidad de Vida , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/psicología , Neoplasias de la Mama/cirugía , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Estudios Prospectivos , Radioterapia Adyuvante , Encuestas y CuestionariosRESUMEN
Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2'-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer.