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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., (© 2021. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. Professors Thompson Robinson and Stephen Walters are National Institute for Health Research (NIHR) Senior Investigators and Jenna Morgan is a NIHR Clinical Lecturer., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Older 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 Methods: A 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., Results: Three 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., Conclusions: The 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 Isrctn: 46099296., Competing Interests: Conflict of interest statement The authors declare no conflict of interest. Professors Stephen Walters and Thompson Robinson are National Institute for Health Research (NIHR) Senior Investigators; Jenna Morgan is a NIHR Clinical Lecturer; and Kate Lifford is funded by the NIHR as part of this project. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Age-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., Methods: Multicentre, 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., Findings: A 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., Interpretation: For 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 Number: ISRCTN: 46099296., Competing Interests: Conflict of interest statement None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Many decisions are made by patients in their last months of life, creating complex decision-making needs for these individuals. Identifying whether currently existing patient decision aids address the full range of these patient decision-making needs will better inform end-of-life decision support in clinical practice., Aims and Design: This systematic review aimed to (a) identify the range of patients' decision-making needs and (b) assess the extent to which patient decision aids address these needs., Data Sources: MEDLINE, PsycINFO and CINAHL electronic literature databases were searched (January 1990-January 2017), supplemented by hand-searching strategies. Eligible literature reported patient decision-making needs throughout end-of-life decision-making or were evaluations of patient decision aids. Identified decision aid content was mapped onto and assessed against all patient decision-making needs that were deemed 'addressable'., Results: Twenty-two studies described patient needs, and seven end-of-life patient decision aids were identified. Patient needs were categorised, resulting in 48 'addressable' needs. Mapping needs to patient decision aid content showed that 17 patient needs were insufficiently addressed by current patient decision aids. The most substantial gaps included inconsistent acknowledgement, elicitation and documentation of how patient needs varied individually for the level of information provided, the extent patients wanted to participate in decision-making, and the extent they wanted their families and associated healthcare professionals to participate., Conclusion: Patient decision-making needs are broad and varied. Currently developed patient decision aids are insufficiently addressing patient decision-making needs. Improving future end-of-life patient decision aid content through five key suggestions could improve patient-focused decision-making support at the end of life.

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*., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Unlabelled: The UK Lung Cancer Screening trial (UKLS) aims to evaluate low-dose computed tomography (LDCT) lung cancer population screening in the United Kingdom. In UKLS, a large population sample ages 50 to 75 years is approached with a questionnaire to determine lung cancer risk. Those with an estimated risk of at least 5% of developing lung cancer in the next 5 years (using the Liverpool Lung project risk model) are invited to participate in the trial. Here, we present demographic, risk, and response rate data from the first 88,897 individuals approached. Of note, 23,794 individuals (26.8% of all approached) responded positively to the initial questionnaire; 12% of these were high risk. Higher socioeconomic status correlated positively with response, but inversely with risk (P < 0.001). The 50- to 55-year age group was least likely to participate, and at lowest cancer risk. Only 5% of clinic attendees were ages ≤60 years (compared with 47% of all 88,897 approached); this has implications for cost effectiveness. Among positive responders, there were more ex-smokers than expected from population figures (40% vs. 33%), and fewer current smokers (14% vs. 17.5%). Of note, 32.7% of current smokers and 18.4% of ex-smokers were designated as high risk. Overall, 1,452 of 23,794 positive responders (6.1%) were deemed high risk and attended a recruitment clinic. UKLS is the first LDCT population screening trial, selecting high-risk subjects using a validated individual risk prediction model., Key Findings: (i) better recruitment from ex- rather than current smokers, (ii) few clinic attendees ages early 50s, and (iii) representative number of socioeconomically deprived people recruited, despite lower response rates.

Aims: Genetically influenced aspects of adolescent behaviour can play a role in alcohol use and peer affiliation. We explored the correlations between friends' alcohol use and adolescent own use with a genetically sensitive design., Design: Genetic and environmental factors were estimated on adolescent reports of their friends' alcohol use and their own use and problem use of alcohol. The correlations between the genetic and environmental factors that influence friends' alcohol use and adolescent own alcohol use and problem use were also estimated., Participants: A total of 862 twin pairs aged 11-17 years sampled from the UK population-based Cardiff Study of All Wales and North-west of England Twins (CaStANET)., Measurements: Data on adolescent own alcohol use and problem use and the alcohol use of their three best friends were obtained using self-report questionnaires., Findings: A significant genetic influence was found on adolescent friends' alcohol use (about 30%). Significant correlations of 0.60 and 0.70 were found between the genetic influences on friends' alcohol use and adolescents' own use and problem use of alcohol. Common environmental influences were almost completely correlated for friends' alcohol use and adolescents' own alcohol use and problem use (0.91 and 0.94)., Conclusions: There is considerable overlap in the common environmental and genetic factors that contribute to the relationship between adolescents' own alcohol use and that of their friends. These findings contribute to understanding of the mechanisms by which friends' alcohol use influences adolescent drinking behaviour.

Aims: To examine the genetic and environmental contributions to the initiation of use and progression to more serious use of alcohol, cigarettes and marijuana during adolescence, and to examine the relationship between initiation and progression of substance use., Design: The study used a twin-based design and a new theoretical model, the causal-common-contingent (CCC) model. This allows modelling of the relationship between initiation of use and progression to heavier use as a two-stage model and the examination of genetic and environmental influences on both stages, while taking into account their relationship., Participants: The participants consisted of 1214 twin pairs (69% response rate) aged 11-19 years sampled from the UK population-based Cardiff Study of All Wales and North-west of England Twins (CaStANET)., Measurements: Data on adolescent initiation and progression to more serious use of alcohol, cigarettes and marijuana were obtained using self-report questionnaires., Findings: Initiation of alcohol and progression to heavier alcohol use had separate but related underlying aetiologies. For cigarette and marijuana use the relation between initiation and progression to heavier use was stronger, suggesting greater overlap in aetiologies. For all three substances, environmental influences that make twins more similar (common environment) tended to be greater for initiation, while genetic influences were stronger for heavier use., Conclusions: These findings have implications for policy decisions aimed at an adolescent and early adult age group. Specifically, these findings suggest that it may be more efficacious to focus alcohol interventions on risk factors for the development of heavier use rather than initiation of use. In contrast, interventions aimed at reducing the initiation of cigarettes and marijuana use may be more appropriate.

The present study used a prospective, longitudinal design to investigate genetic and environmental influences on the association between earlier conduct problems and the initiation and progression of marijuana use during adolescence. Parent- and teacher-reported conduct problems assessed at Time 1 (1996) and self-reported marijuana use assessed at Time 2 (2004) were available for 1088 adolescent twin pairs participating in the Cardiff Study of All Wales and North West of England Twins (CaStANET). Using a novel approach to the modeling of initiation and progression dimensions in substance use, findings suggested that the initiation of marijuana use in adolescence was influenced by genetic, common and unique environmental factors. The progression (or frequency) of marijuana use was influenced by genetic and unique environmental factors. Findings for conduct problems indicated that while the presence or absence of conduct problems was largely heritable, the relative severity of conduct problems appeared to be more strongly environmentally influenced. Multivariate model fitting indicated that conduct problems in childhood and early adolescence made a small but significant contribution to the risk for marijuana use 8 years later.

Objective: The purpose of this study was to identify risk factors for urinary incontinence in middle-aged women., Study Design: We conducted a cross-sectional analysis of 83,355 Nurses' Health Study II participants. Since 1989, women have provided health information on mailed questionnaires; in 2001, at the ages 37 to 54 years, information on urinary incontinence was requested. We examined adjusted odds ratios of incontinence using logistic regression., Results: Forty-three percent of the women reported incontinence. After adjustment, black (odds ratio, 0.49; 95% CI, 0.40-0.60) and Asian-American women (odds ratio, 0.57; 95% CI, 0.46-0.72) were at reduced odds of severe incontinence compared with white women. Increased age, body mass index, parity, current smoking, type 2 diabetes mellitus, and hysterectomy all were associated positively with incontinence. Women who were aged 50 to 54 years had 1.81 times the odds of severe incontinence compared with women who were <40 years old (95% CI, 1.66-1.97); women with a body mass index of > or =30 kg/m2 had 3.10 times the odds of severe incontinence compared with a body mass index of 22 to 24 kg/m2 (95% CI, 2.91-3.30)., Conclusion: Urinary incontinence is highly prevalent among these middle-aged women. Potential risk factors include age, race/ethnicity, body mass index, parity, smoking, diabetes mellitus, and hysterectomy.

Objective: The purpose of this study was to better understand associations among age, race, obstetric history, and urinary incontinence in women., Study Design: Race and obstetric history were assessed through the use of biennial mailed questionnaires from 1976 to 1996 among participants of the Nurses' Health Study. In 1996, 83,168 women aged 50 to 75 years reported their frequency of leaking urine and quantity leaked. We used logistic regression to calculate multivariate-adjusted odds ratios and 95% CIs for the relation of risk factors to leaking urine., Results: Overall, 34.1% of the women reported leaking urine at least once per month during the previous 12 months; this prevalence was lowest in the black women (21.2%). After potential confounders were controlled, there were strong trends of increasing prevalence of occasional and frequent leaking with increasing age (P trend <.0001). There was also increasing prevalence of leaking urine with increasing parity; for example, compared with nulliparous women, the odds ratio for frequent leaking was 1.72 (95% CI, 1.55-1.90) among those with >/=5 births. Odds ratios that were associated with parity were higher in women aged <60 years than in women aged >/=60 years. Age at first birth of >35 years was associated with a slight elevation in frequent leaking compared with women with age at first birth from 21 to 25 years but was stronger for women with age at first birth of <21 years (OR, 1.27; 95% CI, 1.13-1.42)., Conclusion: In these women, leaking urine is common; this condition is most prevalent in white women, in older women, in parous women, and in women with a younger age at first birth.