Time‐Varying Hormonal Treatment and Metastasis‐Free Survival Among ER+ Breast Cancer Patients: A Natural History Modelling Approach

ABSTRACT Breast cancer treatment depends on tumour subtypes. In particular, patients with oestrogen receptor‐positive (ER+) tumours are treated with hormonal therapy. In Sweden, the recommended treatment duration is five years, with current guidelines advising an additional five years for women at high risk of disease recurrence. However, the impact of extended therapy on metastatic progression has not been thoroughly quantified at the population level. In this article, we use a modelling approach to estimate the time‐varying effect of hormonal treatment on time to metastasis. The model is then used to compare 5‐ and 10‐year treatment durations at different tumour sizes. Rather than using a common statistical modelling approach, we incorporate the effect of endocrine therapy within a biologically inspired natural history model of breast cancer to accommodate key features of the expected treatment‐outcome relationship. We fitted the model using maximum likelihood and data from a cohort of 9,716 incident cases diagnosed with invasive ER+ breast cancer between 2005 and 2020. Based on our main model estimates, the 10‐year metastasis‐free survival would improve from 92.8% to 96.1% for a symptomatic patient with a 20 mm tumour with ten years (instead of five) of hormonal treatment. Our natural history model quantifies the impact of prolonged hormonal treatment on metastatic events in ER+ breast cancer patients, including features that are not captured by traditional statistical approaches. Results suggest a significant reduction in metastatic tumour growth rates during treatment, supporting the extension of endocrine therapy to 10 years for people with large tumours.