Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Background In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise reduced treatment tolerance benefit. This may contribute to inferior outcomes. There are currently no age- fitness-stratified guidelines which base recommendations. Aim We aimed optimise choice outcomes for (aged ≥ 70 years) operable cancer. Objectives Our objectives were (1) determine age, comorbidity, frailty, disease stage biology thresholds endocrine therapy alone versus plus adjuvant therapy, or chemotherapy, cancer; (2) survival by improving quality decision-making; (3) develop evaluate a decision support intervention enhance shared (4) degree causes between UK units. Design A prospective cohort study was used age fitness allocation. Mixed-methods research information needs intervention. cluster-randomised trial impact this choices Health economic analysis cost–benefit ratio different strategies according criteria. mixed-methods in Main outcome measures The main enhanced fitness-specific leading improved quality-of-life early Results Cohort study: recruited 3416 aged years (median 77 years). Follow-up 52 months. (a) comparison: 2854 out (88%) had oestrogen-receptor-positive cancer, 2354 whom received 500 alone. Patients treated frailer patients therapy. Unmatched overall breast-cancer-specific higher group (overall survival: hazard 0.27, 95% confidence interval 0.23 0.33; p < 0.001; 0.41, 0.29 0.58; 0.001) group. matched analysis, still associated better (hazard 0.72, 0.53 0.98; = 0.04) alone, but not 0.74, 0.40 1.37; 0.34) progression-free-survival 1.11, 0.55 2.26; 0.78). (b) 2811 (82%) 1520 (54%) high-recurrence-risk [grade 3, node positive, oestrogen receptor negative human epidermal growth factor receptor-2 high Oncotype DX ® (Genomic Health, Inc., Redwood City, CA, USA) score > 25]. high-risk population, there differences use after propensity matching. Adjuvant risk metastatic recurrence unmatched (adjusted 0.36, 0.19 0.68; 0.002) propensity-matched 0.43, 0.20 0.92; 0.03). oestrogen-receptor-negative disease. intervention: an iterative process two interventions (each comprising brief aid, booklet online tool) specifically facing (endocrine chemotherapy) using several evidence sources (expert opinion, literature patient interviews). tool models developed registry data from 23,842 validated external set 14,526 patients. Mortality at 2 5 differed 1% predicted observed values. Cluster-randomised clinical tools: 46 units randomised (intervention, n 21; usual care, 25), recruiting 1339 670; 669). significant difference global life 6 months post baseline (difference –0.20, –2.7 2.3; 0.90). offered knowledge about treatments greater arm care (94% vs. 74%; 0.003). Treatment altered, arm. Similarly, rate: sites 21% usual-care 15%, 5.5%, 1.1% 10.0%; 0.02; 10% site 4.5%, 0.0% 8.0%; 0.013). Survival similar both arms. analysis: probabilistic model data. For most health strata, costs returned more quality-adjusted life-years However, some 90 years, longer cost-effective generated fewer incremental benefit comorbidities. (5) Variation practice: 56 demonstrated that persisted adjustment stage. Clinician preference important determinant choice. Conclusions demonstrates that, expectancy 4 offer little simply have life. Age Gap help make decision. although offers has majority beneficial. impacts life, significant, transient. implies fitter standard should be offered. Limitations As any observational study, despite detailed matching, residual bias cannot excluded. median analysis. Longer-term follow-up will required validate these findings owing slow time course Future work algorithm now available (URL: https://agegap.shef.ac.uk/ ; accessed May 2022). plans incorprate 10-year Trial registration registered as ISRCTN46099296. Funding project funded National Institute Care Research (NIHR) Programme Grants Applied programme published full Vol. 10, No. 6. See NIHR Journals Library website further information.