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As many countries experience population aging, patients with cancer are becoming older and have more preexisting comorbidities, which include prevalent, age-related, chronic conditions such as dementia. People living with dementia (PLWD) are vulnerable to health disparities, and dementia has high potential to complicate and adversely affect care and outcomes across the cancer trajectory. This report offers an overview of dementia and its prevalence among patients with cancer and a summary of the research literature examining cancer care for PLWD. The reviewed research indicates that PLWD are more likely to have cancer diagnosed at an advanced stage, receive no or less extensive cancer treatment, and have poorer survival after a cancer diagnosis. These cancer disparities do not necessarily signify inappropriately later diagnosis or lower treatment of people with dementia as a group, and they are arguably less feasible and appropriate targets for care optimization. The reviewed research indicates that PLWD also have an increased risk of cancer-related emergency presentations, lower quality processes of cancer-related decision making, accessibility-related barriers to cancer investigations and treatment, higher experienced treatment burden and higher caregiver burden for families, and undertreated cancer-related pain. The authors propose that optimal cancer care for PLWD should focus on proactively minimizing these risk areas and thus must be highly person-centered, with holistic decision making, individualized reasonable adjustments to practice, and strong inclusion and support of family carers. Comprehensive recommendations are made for clinical practice and future research to help clinicians and providers deliver best and equitable cancer care for PLWD and their families.
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Demencia , Neoplasias , Humanos , Demencia/complicaciones , Demencia/diagnóstico , Demencia/terapia , Cuidadores , Neoplasias/complicaciones , Neoplasias/terapiaRESUMEN
For several years, a growing number of studies have highlighted the pivotal role of placental extracellular vesicles (EVs) throughout pregnancy. These membrane nanovesicles, heterogeneous in nature, composition and origin, are secreted by several trophoblastic cell types and are found in both the maternal and fetal compartments. They can be uptaken by recipient cells and drive a wide variety of physiological and pathological processes. In this review, we provide an overview of the different described roles of placental EVs in various aspects of normal pregnancy, from placenta establishment to maternal immune tolerance towards the fetus and protection against viral infections. In the second part, we present selected examples of pathological pregnancies in which placental EVs are involved, such as gestational diabetes mellitus, pre-eclampsia, and congenital infections. Since the abundance and/or composition of placental EVs is deregulated in maternal serum during pathological pregnancies, this makes them interesting candidates as non-invasive biomarkers for gestational diseases and opens a wide field of translational perspectives.
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Vesículas Extracelulares , Preeclampsia , Embarazo , Femenino , Humanos , Placenta/metabolismo , Vesículas Extracelulares/metabolismo , Preeclampsia/metabolismo , Preeclampsia/patología , Trofoblastos/metabolismo , ComunicaciónRESUMEN
BACKGROUND: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. RESULTS: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19-0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20-0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08-0.49];BCSS: HR 0.12 [95% CI 0.03-0.44]).Transient negative quality-of-life impacts were observed. CONCLUSIONS: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. TRIAL REGISTRATION: ISRCTN 46099296.
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Antraciclinas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Calidad de Vida/psicología , Taxoides/uso terapéutico , Trastuzumab/uso terapéutico , Anciano , Anciano de 80 o más Años , Antraciclinas/efectos adversos , Neoplasias de la Mama/psicología , Hidrocarburos Aromáticos con Puentes/efectos adversos , Quimioterapia , Femenino , Humanos , Satisfacción del Paciente/estadística & datos numéricos , Puntaje de Propensión , Estudios Prospectivos , Análisis de Supervivencia , Taxoides/efectos adversos , Trastuzumab/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: HIV-1 group O (HIV-1/O) is one of the four HIV-1 groups and is endemic in Cameroon, representing 1% of HIV-1 infections in the population. Around 50% of the strains of this group naturally show a mutation (Y181C) providing them with resistance to NNRTIs and making therapeutic management more difficult. Today, the WHO recommends the use of integrase strand transfer inhibitors (INSTIs) as first-line treatment. Bictegravir and cabotegravir are the two most recent INSTIs. Because of the genetic polymorphism of HIV-1/O, studies are required to evaluate their phenotypic susceptibility to these two drugs. PATIENTS AND METHODS: We performed a phenotypic study on a large panel including 41 HIV-1/O clinical isolates and other rare non-group M HIV-1 (2 HIV-1/N and 1 HIV-1/P) to evaluate in vitro susceptibility to bictegravir and cabotegravir. RESULTS: The results showed an overall susceptibility of non-group M strains to the two drugs compared with HIV-1 group M. There was no difference between the mean (min-max) IC50 of HIV-1/M [1.86 (0.93-4.12) and 5.24 (1.76-12.41) nM for bictegravir and cabotegravir, respectively] and HIV-1/non-M [2.17 (0.03-9.47) and 4.88 (0.02-15.64) nM for bictegravir and cabotegravir, respectively]. However, we found a significant difference between IC50 values for bictegravir and cabotegravir in the whole panel (P value <â0.001). CONCLUSIONS: This study has shown encouraging results regarding the clinical use of these drugs in HIV-1/non-M-infected patients, which will need to be confirmed with clinical data.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , VIH-1 , Amidas , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/genética , Compuestos Heterocíclicos con 3 Anillos , Humanos , Piperazinas , Piridonas/farmacologíaRESUMEN
Nitric oxide (NO) deficiency is often associated with several acute and chronic diseases. NO donors and especially S-nitrosothiols such as S-nitrosoglutathione (GSNO) have been identified as promising therapeutic agents. Although their permeability through the intestinal barrier have recently be proved, suitable drug delivery systems have to be designed for their oral administration. This is especially challenging due to the physico-chemical features of these drugs: high hydrophilicity and high lability. In this paper, three types of particles were prepared with an Eudragit® polymer: nanoparticles and microparticles obtained with a water-in-oil-in-water emulsion/evaporation process versus microparticles obtained with a solid-in-oil-in-water emulsion/evaporation process. They had a similar encapsulation efficiency (around 30%), and could be freeze-dried then be stored at least one month without modification of their critical attributes (size and GSNO content). However, microparticles had a slightly slower in vitro release of GSNO than nanoparticles, and were able to boost by a factor of two the drug intestinal permeability (Caco-2 model). Altogether, this study brings new data about GSNO intestinal permeability and three ready-to-use formulations suitable for further preclinical studies with oral administration.
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Portadores de Fármacos/química , Nanopartículas/química , Donantes de Óxido Nítrico/farmacología , S-Nitrosoglutatión/farmacología , Células CACO-2 , Portadores de Fármacos/toxicidad , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Liofilización , Humanos , Mucosa Intestinal/metabolismo , Nanopartículas/toxicidad , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/química , Donantes de Óxido Nítrico/toxicidad , Tamaño de la Partícula , S-Nitrosoglutatión/química , S-Nitrosoglutatión/toxicidadRESUMEN
OBJECTIVE: To explore how caregivers are involved in making treatment decisions for older people living with dementia and a new diagnosis of cancer. METHOD: A systematic review of PubMed, CINAHL, PsycINFO, Web of Science, and Scopus databases was conducted. Studies recruiting formal or informal caregivers for older people with dementia and a diagnosis of cancer were considered for inclusion. RESULTS: Of 1761 articles screened, 36 full texts were assessed for eligibility, and six were included in the review. This review has identified that health care professionals (HCPs) are often unaware of the coexistence or severity of dementia in cancer patients, and therefore fail to properly address care needs as a result. While caregivers are relied on to help make decisions, they have unmet information needs and feel excluded from decision-making. CONCLUSION: Treatment decision making in the context of older adults with dementia and a new diagnosis of cancer needs further research. This will help HCPs to understand their needs and improve the experience of decision making for both caregivers and the people that they care for.
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Cuidadores , Toma de Decisiones Clínicas , Toma de Decisiones Conjunta , Demencia/terapia , Neoplasias/terapia , Relaciones Profesional-Familia , Demencia/enfermería , Humanos , Neoplasias/enfermeríaRESUMEN
OBJECTIVE: Patients with cancer face difficult decisions regarding treatment and the possibility of trading quality of life (QoL) for length of life (LoL). Little information is available regarding patients' preferences and attitudes toward their cancer treatment and the personal costs they are prepared to exchange to extend their life. The aim of this review is to determine the complex trade-offs and underpinning factors that make patients with cancer choose quality over quantity of life. METHODS: A systematic review of the literature was conducted using MeSH terms: cancer, longevity or LoL, QoL, decision making, trade-off, and health utility. Articles retrieved were published between 1942 and October 2018. RESULTS: Out of 4393 articles, 30 were included in this review. Older age, which may be linked to declining physical status, was associated with a preference for QoL over LoL. Younger patients were more likely to undergo aggressive treatment to increase survival years. Preference for QoL and LoL was not influenced by gender, education, religion, having children, marital status, or type of cancer. Patients with better health valued LoL and inversely those with poorer physical status preferred QoL. CONCLUSION: Baseline QoL and future expectations of life seem to be key determinants of preference for QoL versus LoL in cancer patients. In-depth studies are required to understand these trade-offs and the compromises patients are willing to make regarding QoL or LoL, especially in older patients with naturally limited life expectancy.
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Neoplasias/psicología , Prioridad del Paciente , Años de Vida Ajustados por Calidad de Vida , Religión y Psicología , Valor de la Vida , Adulto , Anciano , Anciano de 80 o más Años , Actitud Frente a la Muerte , Toma de Decisiones , Femenino , Humanos , Longevidad , Masculino , Persona de Mediana Edad , Satisfacción del PacienteAsunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Alanina/uso terapéutico , Amidas , Fármacos Anti-VIH/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Piperazinas , Piridonas/uso terapéutico , Tenofovir/análogos & derivadosRESUMEN
BACKGROUND: This study reports the detailed management and outcomes of women treated with Primary Endocrine Therapy (PET) in a large prospective UK cohort of older women (≥70) with breast cancer. METHODS: This was an unplanned secondary analysis of a prospective, multicentre, observational study (The Age Gap study). Data were collected at baseline and regular intervals on patient, tumour and treatment characteristics with tumour RECIST response category recorded. Direct study follow-up was 24 months with longer-term survival data obtained from the UK cancer registry. RESULTS: The Age Gap study recruited 3316 women across 56 breast units. Primary endocrine therapy (PET) was initiated for 505/3316 (15 %) women; median age was 84 (IQR 79-88) with median follow-up 41.9 months (IQR 27-60). Death occurred in 205/505(40.6 %) patients, 160/205; 78 % non- Breast Cancer related, 45/205; 21.9 % Breast Cancer related. Multivariate analysis identified older age (HR-1.055(95 % Confidence Interval: 1.029-1.084); P < 0.001) and higher Charlson Index (HR-1.166 (1.086-1.252); P < 0.001) as risk factors for all-cause mortality, but conversion to surgery (HR-0.372(0.152-0.914); P = 0.031) was protective. Grade 3 cancer (G1 vs G3 HR-0.28 (0.094-0.829); P = 0.022 & G2 vs G3 HR-0.469 (0.226-0.973); P = 0.042), axillary positivity (axilla positivity HR-2.548 (1.321-4.816); P = 0.005) and change of endocrine therapy (HR-3.010 (1.532-5.913); P = 0.001) were associated with worse breast cancer specific survival (BCSS). RECIST category was not significantly associated with either overall survival or BCSS (P > 0.05). CONCLUSION: Early disease response and change of endocrine therapy are not significantly associated with overall survival, conversion to surgery is linked to improved outcome. Prognosis is largely determined by age and comorbidity in older women treated with PET.
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The susceptibility of genetically divergent HIV-1 strains (HIV-1 non-M) from groups O, N, and P to the CCR5 co-receptor antagonist, maraviroc (MVC), was investigated among a large panel of 45 clinical strains, representative of the viral genetic diversity. The results were compared to the reference strains of HIV-1 group M (HIV-1/M) with known tropism. Among the non-M strains, a wide range of phenotypic susceptibilities to MVC were observed. The large majority of HIV-1/O strains (40/42) displayed a high susceptibility to MVC, with median and mean IC50 values of 1.23 and 1.33 nM, respectively, similar to the HIV-1/M R5 strain (1.89 nM). However, the two remaining HIV-1/O strains exhibited a lower susceptibility (IC50 at 482 and 496 nM), in accordance with their dual/mixed (DM) tropism. Interestingly, the two HIV-1/N strains demonstrated varying susceptibility patterns, despite always having relatively low IC50 values (2.87 and 47.5 nM). This emphasized the complexity of determining susceptibility solely based on IC50 values. Our study examined the susceptibility of all HIV-1 non-M groups to MVC and correlated these findings with virus tropism (X4, R5, or DM). The results confirm the critical significance of tropism determination before initiating MVC treatment in patients infected with HIV-1 non-M. Furthermore, we advocate for the consideration of additional parameters, such as the slope of inhibition curves, to provide a more thorough characterization of phenotypic susceptibility profiles. IMPORTANCE: Unlike HIV-1 group M, the scarcity of studies on HIV-1 non-M groups (O, N, and P) presents challenges in understanding their susceptibility to antiretroviral treatments, particularly due to their natural resistance to non-nucleoside reverse transcriptase inhibitors. The TROPI-CO study logically complements our prior investigations into integrase inhibitors and anti-gp120 efficacy. The largest panel of 45 non-M strains existing so far yielded valuable results on maraviroc (MVC) susceptibility. The significant variations in MVC IC50 reveal a spectrum of susceptibilities, with most strains displaying R5 tropism. Notably, the absence of MVC-resistant strains suggests a potential therapeutic avenue. The study also employs a robust novel cell-based phenotropism assay and identifies distinct groups of susceptibilities based on inhibition curve slopes. Our findings emphasize the importance of determining tropism before initiating MVC and provide crucial insights for selecting effective therapeutic strategies in the delicate context of HIV-1 non-M infections.
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Antagonistas de los Receptores CCR5 , Infecciones por VIH , VIH-1 , Maraviroc , Tropismo Viral , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/fisiología , Maraviroc/farmacología , Humanos , Antagonistas de los Receptores CCR5/farmacología , Infecciones por VIH/virología , Infecciones por VIH/tratamiento farmacológico , Concentración 50 Inhibidora , Triazoles/farmacología , Fenotipo , Pruebas de Sensibilidad Microbiana , Receptores CCR5/metabolismo , Receptores CCR5/genética , Fármacos Anti-VIH/farmacología , Ciclohexanos/farmacología , Farmacorresistencia Viral/genética , Inhibidores de Fusión de VIH/farmacologíaRESUMEN
INTRODUCTION: Increased moderate to vigorous physical activity (MVPA) can improve clinical and psychosocial outcomes for people living with and beyond cancer (LWBC). This study aimed to assess the feasibility and acceptability of trial procedures in a pilot randomised controlled trial (RCT) of a theory-driven app-based intervention with behavioural support focused on promoting brisk walking (a form of MVPA) in people LWBC (APPROACH). METHODS: Participants diagnosed with breast, prostate or colorectal cancer were recruited from a single UK hospital site. Assessments at baseline and 3 months included online questionnaires, device-measured brisk walking (activPAL accelerometer) and self-reported weight and height. Participants were randomised to intervention or control (care as usual). The intervention comprised a non-cancer-specific app to promote brisk walking (National Health Service 'Active 10') augmented with print information about habit formation, a walking planner and two behavioural support telephone calls. Feasibility and acceptability of trial procedures were explored. Initial estimates for physical activity informed a power calculation for a phase III RCT. A preliminary health economics analysis was conducted. RESULTS: Of those medically eligible, 369/577 (64%) were willing to answer further eligibility questions and 90/148 (61%) of those eligible were enrolled. Feasibility outcomes, including retention (97%), assessment completion rates (>86%) and app download rates in the intervention group (96%), suggest that the trial procedures are acceptable and that the intervention is feasible. The phase III RCT will require 472 participants to be randomised. As expected, the preliminary health economic analyses indicate a high level of uncertainty around the cost-effectiveness of the intervention. CONCLUSIONS: This pilot study demonstrates that a large trial of the brisk walking intervention with behavioural support is both feasible and acceptable to people LWBC. The results support progression onto a confirmatory phase III trial to determine the efficacy and cost-effectiveness of the intervention.
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Neoplasias Colorrectales , Aplicaciones Móviles , Masculino , Humanos , Próstata , Estudios de Factibilidad , Caminata , Reino Unido , Neoplasias Colorrectales/terapiaRESUMEN
The role of extracellular vesicles (EVs) as key players in the intercellular communication is a subject of growing interest in all areas of physiology and pathophysiology, and the field of viral infections is no exception to the rule. In this review, we focus on the current state of knowledge and remaining gaps regarding the entanglement of viruses and EVs during infections. These two entities share many similarities, mainly due to their intricated biogenesis pathways that are in constant interaction. EVs can promote the replication and dissemination of viruses within the organism, through the dysregulation of their cargo and the modulation of the innate and adaptive immune response that occurs upon infection, but they can also promote the mitigation of viral infections. Here, we will examine how viruses hijack EV biogenesis pathways and describe the consequences of dysregulated EV secretion during viral infections, beneficial or not for viruses, revealing the duality of their possible effects.
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KEY WORDS: Breast cancer, mastectomy, breast conserving surgery, post-mastectomy reconstruction, older women, quality of life.
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Neoplasias de la Mama , Mamoplastia , Femenino , Humanos , Anciano , Mastectomía , Neoplasias de la Mama/cirugía , Estudios de Cohortes , Calidad de Vida , Mastectomía SegmentariaRESUMEN
Family caregivers are an important source of support for older people living with dementia, especially when faced with a new diagnosis of cancer. Little is currently known about the caregiver role in facilitating treatment discussions, and the factors that underpin breast cancer treatment decision-making in older patients. This study used a sequential explanatory mixed method approach to explore the role of family caregivers in making cancer treatment decisions for older women (aged over 70 years) with pre-existing dementia and primary operable breast cancer. Thirteen caregivers participated in the study (13 completed a postal questionnaire; eight questionnaire respondents participated in a semi-structured interview). Quantitative data were analysed descriptively, and the Framework Approach was used to analyse qualitative findings and identify themes. Three themes were generated: (a) Clinical interactions, information and support; (b) Treatment decision-making processes and (c) Influences on treatment choice. These findings highlight the complexities that caregivers face when navigating cancer treatment options and their role in facilitating treatment decisions.
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Neoplasias de la Mama , Demencia , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Cuidadores , Toma de Decisiones , Demencia/diagnóstico , Demencia/terapia , Femenino , HumanosRESUMEN
BACKGROUND: Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. OBJECTIVES: We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. METHODS: Women diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. RESULTS: 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0-81.0) and 75.0 (IQR: 72.0-81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9-5.4) in Age Gap and 4.3 years (IQR 2.9-5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74-1.17, p = 0.568). CONCLUSIONS: In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.
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Neoplasias de la Mama , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Países Bajos/epidemiología , Estudios Prospectivos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: In the UK there is variation in the treatment of older women with breast cancer, with up to 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and patient choice may explain some variation in practice but clinician preference may also be important. METHODS: A multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making preference) were analysed to identify whether treatment variation persisted following case-mix adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, co-morbidity, tumour stage and grade. Concordance between patients' preferred and actual decision-making style was assessed and associations between age, treatment and decision-making style calculated. RESULTS: Women (median age 77, range 70-102) were recruited from 56 UK breast units between 2013 and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56 units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients (42.2% vs 28.4%, pâ¯<â¯0.001). CONCLUSIONS: This study demonstrates variation in treatment selection thresholds for older women with breast cancer. Health stratified guidelines on thresholds for PET would help reduce variation, although patient preference should still be respected.
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Neoplasias de la Mama/terapia , Terapia de Reemplazo de Hormonas/métodos , Mastectomía/métodos , Selección de Paciente , Factores de Edad , Anciano , Anciano de 80 o más Años , Conducta de Elección , Femenino , Estudios de Seguimiento , Humanos , Prioridad del Paciente , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Recruitment and retention are two of the most important factors in successfully running clinical trials. Many trials encounter problems with both, causing delays or preventing study progress. These issues are greater in older adults and patients with cancer. MATERIALS AND METHODS: We assessed recruitment and retention in a large, multicentre, observational breast cancer study in older female patients (>70 years, N = 3440). Data collected by the Age Gap study were used to assess rates of, and reasons for, patients not being recruited or retained. Statistical analysis assessed the impact of age as a predictor of recruitment and retention. RESULTS: Between February 2013 and June 2018, 6876 patients were screened and 3456 were consented across 56 United Kingdom (UK) breast units. Reasons for non-recruitment included ineligibility, clinician issues, staffing resource issues, patients' lack of interest or time and trial burden. In comparison with the age demographics of patients with breast cancer in the UK, women aged 70-75 years were over-represented compared to older age groups. Logistic regression demonstrated that older age significantly reduced the odds of consent (OR = 0.96, CI: 0.938-0.982; p < 0.001). Multivariate analysis showed that age (p < 0.001), markers of poor functional ability (Eastern Cooperative Oncology Group Performance Status (p = 0.011)) and instrumental activities of daily living (p = 0.026) were significant predictors of withdrawal. DISCUSSION: This study has demonstrated that selection and attrition bias for age are apparent despite a range of 'age friendly' study design measures. Exploration of the underlying reasons for this and development of measures to address this should be the focus of further research.
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Neoplasias de la Mama , Actividades Cotidianas , Anciano , Neoplasias de la Mama/terapia , Femenino , Humanos , Modelos Logísticos , Proyectos de Investigación , Reino UnidoRESUMEN
OBJECTIVES: The presence of dementia co-existing with a diagnosis of breast cancer may render management more challenging and have a substantial impact on oncological outcomes. The aim of this study was to examine the treatment and outcomes of older women with co-existing cognitive impairment and primary breast cancer. MATERIALS AND METHODS: A prospective, multicentre UK cohort study of women aged 70 years or over with primary operable breast cancer. Patients with and without cognitive impairment were compared to assess differences in treatment and survival outcomes. RESULTS: In total, 3416 women were recruited between 2013 and 2018. Of these, 478 (14%) had a diagnosis of dementia or cognitive impairment, subcategorised as mild, moderate and severely impaired. Up to 85% of women with normal cognition underwent surgery compared to 74%, 61% and 40% with mild, moderate, and severe impairment (p = 0.001). Among women at higher risk of recurrence, the uptake of chemotherapy was 25% for cognitively normal women compared to 20%, 22% and 12% for mild, moderate and severe impairment groups (p = 0.222). Radiotherapy use was similar in the subgroups. Although patients with cognitive impairment had shorter overall survival (HR: 2.10, 95% CI: 1.77-2.50, p < 0.001), there were no statistically significant differences in breast cancer specific or progression-free survival. CONCLUSION: Cognitive impairment appears to play a significant part in deciding how to treat older women with breast cancer. Standard treatment may be over-treatment for some women with severe dementia and careful consideration must be given to a more tailored approach in these women.
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Neoplasias de la Mama , Disfunción Cognitiva , Anciano , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Disfunción Cognitiva/etiología , Estudios de Cohortes , Femenino , Humanos , Recurrencia Local de Neoplasia , Estudios ProspectivosRESUMEN
BACKGROUND: Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL). METHODS: A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: In 2013-2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months. CONCLUSION: Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient.