Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.
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ABSTRACT: 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.
SUBMITTER: Ring A
PROVIDER: S-EPMC8292504 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionOlder patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study.Materials and methodsA prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013-2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching.ResultsThree thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18-24 months in unmatched and matched cohorts.ConclusionsThe negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy.Trial registration number isrctn46099296.
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Project description:IntroductionRecruitment 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 methodsWe 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.ResultsBetween 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.DiscussionThis 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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Project description:INTRODUCTION:While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. METHODS AND ANALYSIS:This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. ETHICS AND DISSEMINATION:National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. IRAS REFERENCE:115550. TRIAL REGISTRATION NUMBER:European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*.
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Project description:BackgroundAge-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET.MethodsMulticentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer. Data on fitness, frailty, cancer stage, grade, biotype, treatment and quality of life were collected. Propensity-matching (based on age, health status and cancer stage) adjusted for allocation bias when comparing S+ET with PET.FindingsA total of 3416 women (median age 77, range 69-102) were recruited from 56 breast units-2854 (88%) had ER+ breast cancer: 2354 had S+ET and 500 PET. Median follow-up was 52 months. Patients treated with PET were older and frailer than patients treated with S+ET. Unmatched overall survival was inferior in the PET group (hazard ratio, (HR) 0.27, 95% confidence interval (CI) 0.23-0.33, P < 0.001). Unmatched breast cancer-specific survival (BCSS) was also inferior in patients treated with PET (HR: 0.41, CI: 0.29-0.58, P < 0.001 for BCSS). In the matched analysis, PET was still associated with an inferior overall survival (HR = 0.72, 95% CI: 0.53-0.98, P = 0.04) but not BCSS (HR = 0.74, 95% CI: 0.40-1.37, P = 0.34) although at 4-5 years subtle divergence of the curves commenced in favor of surgery. Global health status diverged at certain time points between groups but over 24 months was similar when adjusted for baseline variance.InterpretationFor the majority of older women with early ER+ breast cancer, surgery is oncologically superior to PET. In less fit, older women, with characteristics similar to the matched cohort of this study (median age 81 with higher comorbidity and functional impairment burdens, the BCSS survival differential disappears at least out to 4-5 year follow-up, suggesting that for those with less than 5-year predicted life-expectancy (>90 years or >85 with comorbidities or frailty) individualised decision making regarding PET versus S+ET may be appropriate and safe to offer. The Age Gap online decision tool may support this decision-making process (https://agegap.shef.ac.uk/).Trial registration numberISRCTN: 46099296.
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Project description:Simple Summary Chemotherapy-induced peripheral neuropathy (CIPN) remains a clinical challenge with a considerable impact on the effective treatment of cancers and quality of life during and after concluding chemotherapy. Given the limited understanding of CIPN, there are no options for the treatment and prevention of CIPN. Decades of research with the unsuccessful translation of preclinical findings to clinical studies argue for the requirement of human model systems. This review focuses on the translational potential of human induced pluripotent stem cells (iPSCs) in CIPN research. We provide an overview of the current studies and discuss important aspects to improve the translation of in vitro findings. We identified distinct effects on the neurite network and cell viability upon exposure to different classes of chemotherapy. Our study revealed considerable variability between donors and between neurons of the central and peripheral nervous system. Translational success may be improved by including multiple iPSC donors with known clinical data and selecting clinically relevant concentrations. Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially serious adverse effect of a wide range of chemotherapeutics. The lack of understanding of the molecular mechanisms underlying CIPN limits the efficacy of chemotherapy and development of therapeutics for treatment and prevention of CIPN. Human induced pluripotent stem cells (iPSCs) have become an important tool to generate the cell types associated with CIPN symptoms in cancer patients. We reviewed the literature for iPSC-derived models that assessed neurotoxicity among chemotherapeutics associated with CIPN. Furthermore, we discuss the gaps in our current knowledge and provide guidance for selecting clinically relevant concentrations of chemotherapy for in vitro studies. Studies in iPSC-derived neurons revealed differential sensitivity towards mechanistically diverse chemotherapeutics associated with CIPN. Additionally, the sensitivity to chemotherapy was determined by donor background and whether the neurons had a central or peripheral nervous system identity. We propose to utilize clinically relevant concentrations that reflect the free, unbound fraction of chemotherapeutics in plasma in future studies. In conclusion, iPSC-derived sensory neurons are a valuable model to assess CIPN; however, studies in Schwann cells and motor neurons are warranted. The inclusion of multiple iPSC donors and concentrations of chemotherapy known to be achievable in patients can potentially improve translational success.
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Project description:Breast cancer is the most common malignant disease and among the most frequent causes of cancer mortality in females worldwide. Metastatic breast cancer (MBC) is conventionally considered to be incurable. In first-line treatment of HER-2 positive MBC, randomized trials have demonstrated that trastuzumab when combined with chemotherapy significantly improves progression free survival and overall survival. To evaluate survival and toxicity of chemotherapy with Trastuzumab as first line therapy of human epithermal growth factor receptor 2 positive metastatic breast cancer, in Moroccan population. It is a phase IV observational institutional monocentric study. Including patients with metastatic breast cancer HER2 positive, as first-line chemotherapy combined with Trastuzumab from March 2009 until March 2010. Primary end point: progression free survival, secondary end point response rate and overall survival. A total of 20 patients were enrolled between March 2009 and March 2010. The lung was the first metastatic site in 60% of the cases, followed by bone, liver, nodes, skin and brain. All patients received chemotherapy with Trastuzumab: 9 of them with Docetaxel, 8 with vinorelbine, and 3 with capecitabine. The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab based chemotherapy was generally well tolerated; 5 patients (25%) presented cardiotoxicity. The results of this study join the literature and show the benefit of Trastuzumab to chemotherapy in first line metastatic breast cancer HER-2 positive.
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Project description:BackgroundWith the increasing global aging population, how to allocate older people care resources reasonably has become an increasingly urgent international issue. China, as the largest developing country, has made many efforts to actively respond to the challenges of an aging population. However, there are still problems with uneven allocation of older people care resources and low efficiency of allocation. Therefore, this study evaluates the regional differences and dynamic evolution of the equity and efficiency of older people care resource allocation in China from 2009 to 2020, and explores ways to change the current situation.MethodsThe data used in this study were derived from the "China Statistical Yearbook" and the "China Civil Affairs Statistical Yearbook" for the period of 2010-2021. Firstly, the equity of older people care resource allocation was measured using the Gini coefficient, the Theil index, the Older People Care Resource Density Index, and the Older People Care Resource Agglomeration Degree. Secondly, the dynamic Slack-Based Measure data envelopment analysis method was adopted to evaluate efficiency. Lastly, the Z-score is used to normalize the equity index and perform classification matching with the efficiency value. Spatial autocorrelation analysis and hotspot analysis were conducted using GIS technology to examine the dynamic evolution process of older people care resource allocation equity and efficiency, as well as their spatial distribution patterns and coordination across provinces from 2009 to 2020.ResultsThe equity analysis showed that the spatial distribution of various types of older people care resources was uneven, and the differences were mainly due to internal differences within each region, with the largest equity differences observed in western provinces. Currently, older people care resources are mainly concentrated in eastern regions, while the total amount of older people care resources in western regions and some central regions is relatively small, which cannot meet the older people care needs of residents. The efficiency analysis results showed that the efficiency of older people care resource allocation has been improving over the past 12 years, and in 2020, 77.42% of provinces were located on the efficiency frontier with an average efficiency value of 0.9396. Finally, the coordination analysis results showed that there were significant spatiotemporal differences in the equity and efficiency of older people care resources allocation.ConclusionWith the development of society and economy, the total amount and service capacity of older people care resources in China have greatly improved. However, there are still significant spatiotemporal differences in the equity and efficiency of older people care resource allocation. The development of older people care services in central and eastern provinces is unbalanced, and there is a polarization trend in terms of equity and efficiency of older people care resource allocation. Most provinces in western regions face the dual dilemma of inadequate older people care resources and low utilization efficiency. It is recommended that policymakers comprehensively consider population and geographic factors in different provinces, establish relevant allocation standards according to local conditions, improve the redistribution system, and focus on increasing the total amount of older people care resources in underdeveloped provinces while promoting resource flow.
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Project description:ObjectivesMost studies of older adults' social networks focus on their access to dense networks that yield access to social support. This paper documents gender differences in the extent to which older adults maintain a related, but distinct, form of social capital-bridging potential, which involves serving as a tie between two unconnected parties and thus boosts independence and control of everyday social life.MethodsI use egocentric social network data from a national sample of 3,005 older adults--collected in 2005-2006 by the National Social Life, Health, and Aging Project--to compare older men's and women's network bridging potential using multivariate regression analysis.ResultsOlder women are more likely than older men to have bridging potential in their networks-between both kin and non-kin contacts. These gender differences increase with age. Older women are also more likely to have network members who are not connected to or monopolized by their spouse or partner. Some, but not all, of these gender differences are due to the fact that older women have larger social networks and maintain more ties to people outside of the household.DiscussionThese findings raise important questions about the relational advantages older women have over older men, including greater autonomy, and contradict stereotypes about women having more closely knit, kin-centered networks than men.
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