Health Economic Impact of Non-Persistence with Tamoxifen Adjuvant Endocrine Therapy in Pre-Menopausal Women with Early-Stage Breast Cancer: A Simulation Study

OBJECTIVES: Low persistence rates with tamoxifen adjuvant endocrine therapy among women with early breast cancer indicate a care gap and potential for improving patient outcomes. However, the permissible cost of strategies addressing this issue at the population level remains unclear. Our study aimed to quantify the burden of suboptimal persistence with tamoxifen in premenopausal women with early breast cancer in terms of healthcare costs and quality-adjusted life years (QALYs).

METHODS: A Markov model was developed to simulate outcomes for premenopausal (age<45), ER+, HER2- early breast cancer patients prescribed 5 years of tamoxifen, from the US societal perspective, over a 10-year time horizon. The model states included Disease-Free, Recurrence, Thromboembolism and Endometrial Cancer (as tamoxifen-related major adverse events), and Death. Costs and QALYs were calculated for current persistence levels (status quo) and a hypothetical full-persistence (5-year) scenario, applying a 3% annual discount rate. Real-world tamoxifen discontinuation rates, health-state utilities, and adverse event probabilities were sourced from literature, and survival and recurrence probabilities from Early Breast Cancer Trialists' Collaborative Group data. Direct and indirect costs in 2022 USD were included. Sensitivity analyses were performed.

RESULTS: The status quo scenario was associated with $297,477 costs and 6.57 QALYs, while the full-persistence scenario had $295,425 costs and 6.74 QALYs. The incremental cost-effectiveness ratio (ICER) of full-persistence compared to status quo was-$11,904/QALY. Considering $100,000/QALY willingness-to-pay, the net monetary benefit (NMB) for changing a non-persistent patient to persistent was $19,287. Probabilistic sensitivity analysis revealed the full-persistence scenario was dominant in 66.0% and cost-effective in 99.4% of iterations. Deterministic sensitivity analysis identified the probability of breast cancer mortality and the recurrence-free utility as key parameters.

CONCLUSIONS: Our study demonstrates the substantial health-related and economic value of improving tamoxifen persistence in premenopausal women with early breast cancer. Implementing strategies to improve tamoxifen persistence can yield a significant return on investment.