Health and Economic Loss of Primary Endocrine Therapy to Older Women with Operable Early-stage Breast Cancer: A Cost-effectiveness and Value of Implementation Analysis

Introduction
A growing number of older women (aged ≥70 years) diagnosed with early-stage breast cancer receive primary endocrine therapy (PET) instead of surgery [1]. However, current national guidelines recommend surgery for all patients if suitable [2]. Understanding the economic impact of using PET with patients suitable for first-line surgery will be valuable evidence to strengthen current national guidelines for operable breast cancer.

Aim
To assess the cost-effectiveness of surgery compared with PET in older women with early-stage breast cancer who are suitable for surgery and the value of improving the uptake of first-line surgery in England.

Method
A probabilistic decision-analytic model-based cost-effectiveness analysis was performed with a Markov model (time horizon: lifetime). Transition probabilities were estimated by parametric survival analysis. Patient-level data were recreated by digitising Kaplan-Meier curves (overall survival and progression-free survival) from the 20-year follow-up of a randomised controlled trial which compared mastectomy with tamoxifen in older women who had operable breast cancer [3]. Health outcomes were measured by quality-adjusted life years (QALYs) using the EQ-5D-3L (UK tariff). Direct costs were measured from the perspective of NHS England. Costs and QALYs were discounted at 3.5% per year. Deterministic analysis, probabilistic sensitivity analyses were conducted to analyse the incremental cost-effectiveness ratio and incremental net monetary benefit (INMB). A value of implementation analysis estimated the QALYs forgone due to imperfect implementation of surgery. The expected value of perfect implementation (EVPImp) was calculated as (1) the difference in the net health benefit for current and perfect uptake of surgery and (2) scaling this QALY loss to the population level. The current uptake of surgery (76% of patients) and the population size (115,309 incident patients with breast cancer or early-stage breast cancer over 10-years in England) was estimated from the 2021 National Audit of Breast Cancer in Older Patients [1]. The analysis assumed a cost-effectiveness threshold of £20,000 per QALY gained.

Results
Surgery was the cost-effective and dominant strategy for older women with operable early-stage breast cancer. The lifetime total cost and QALYs of surgery were £28,424 and £5 per patient. The lifetime total cost and QALYs of PET were approximately £53,714 and £34 per patient. The surgery's INMB was approximately £44,636 (cost-effectiveness threshold: £20,000 per QALY gained). Imperfect implementation of surgery resulted in a loss of 0.5 QALYs per patient. When scaled to the population level, this resulted in a population EVPImp of 62,266 QALYs.

Conclusion
The findings of this study strengthen current national guidelines for managing breast cancer in older women. Surgery is a cost-effective way to treat operable early-stage breast cancer, compared with PET alone, in patients aged 70 and above. The use of PET by this group of patients can negatively impact population health and health care resource use. Activities to improve the uptake of surgery or explain the economic trade-offs between PET and surgery in shared decision-making, will be valuable to undertake in the future.