Quantifying the Clinical and Cost-Effectiveness of Primary Endocrine Therapy Compared with Surgery for Oestrogen Receptor Positive Breast Cancer in Older Women

Abstract

The increasing number of women diagnosed with breast cancer at an older age (at and over 70 years) led to challenges in optimising treatment strategies for this population. Surgery is the recommended first-line treatment for women with early-stage breast cancer in England. In contrast, primary endocrine therapy (PET) is suggested for patients with oestrogen receptor-positive and shorter life expectancy who are unfit for surgery due to frailty or co-morbidity. However, PET has been widely used as an alternative to surgery for older women with oestrogen receptor-positive (ER+) early-stage breast cancer. The synthesised data of seven randomised controlled trials indicated no statistical difference in overall survival between surgery and PET for treating older patients who are physically fit for surgery. However, limited comparative effectiveness data compares these two treatments in the real world. Besides, there is a lack of economic evidence to inform the cost-effectiveness of PET versus surgery in older women with early-stage breast cancer. This thesis aimed to generate economic evidence of PET versus surgery in older women with oestrogen receptor-positive early-stage breast cancer to inform the healthcare decision-making by clinicians, patients and policymakers. Five individual studies were conducted sequentially to fulfil the thesis aim, including (1) two systematic reviews to appraise current evidence sources estimating input parameters used in model-based economic evaluations in postmenopausal women with primary breast cancer and (2) to estimate health state utility values of women with breast cancer and their correlation with age; (3) a lifetime Markov model with six-month cycle length based on randomised control trials comparing the cost-effectiveness and value of the implementation of PET versus surgery in older patients who were physically fit for surgery from the perspective of National Health Service (NHS) England and Personal Social Services using the 2020/21 prices; (4) a cohort study using a large longitudinal datalink in England to investigate the impact of frailty and comorbidity on the comparative clinical effectiveness of PET versus surgery; (5) a same model-based economic evaluation of PET versus surgery for older women with early-stage breast cancer who are frail and potentially unfit for surgery. In line with the national recommendation for operable women with breast cancer, surgery is still a cost-effective use of healthcare resources for older patients who are fit for surgery or have minor physical issues (i.e., pre-frail) based on current evidence. The results indicated that PET had a higher cost (£27,459.51) and more QALYs gained (0.16), translating them into the ICER was £173,395.82 per QALY gain. The cohort study demonstrated that the hazard ratios of breast cancer-specific mortality comparing PET with surgery reduced from 3.0 (95%CI: 2.8, 3.2) in older patients at the non-frail level to 1.2 (95%CI: 0.9, 1.8) at the frail level; and from 3.0 (95%CI: 2.8, 3.3) at the low CCI level to 1.5 (95%CI: 1.1, 2.1) at the high CCI level. Based on the findings of the cohort study, a further economic evaluation was indicated for the patients who are at high levels of HFRS. PET is a cost-effective strategy with an incremental cost and QALYs of £7,351.48 and 0.38, translating into the ICER of £19,498.08 per QALY gain. The value of information analysis indicated it was valuable to conduct further research. Specifically, further evidence on the clinical effectiveness of interventions for older patients who are physically unfit for surgery (i.e., patients with frailty or multiple comorbidities) is required. This thesis highlighted that PET is a potentially cost-effective strategy for frail older patients in the UK, and surgery is still a first-line strategy for older patients who are physically fit for surgery or have mild-moderate frailty.

Date of Award	31 Dec 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Li-Chia Chen (Supervisor), Douglas Steinke (Supervisor) & Sean Gavan (Supervisor)