Explaining the Relationships Between Age, Endocrine Therapy Persistence, and Risk of Recurrence in Hormone Receptor–Positive Early Breast Cancer: A Nationwide Cohort Study

Young age is associated with increased risk of recurrence in hormone receptor (HR)-positive early-stage breast cancer (eBC). Lack of adherence to endocrine therapy (ET) is a potential reason for the lower survival proportions observed in younger patients, but the survival benefits of improving adherence to ET in young patients remain unknown. Using data from the French National Health Data System and target trial emulation methods, we considered three sustained ET persistence strategies (allowing treatment gaps of no more than 30, 90, or 180 continuous days) and estimated the 5-year disease-free survival (DFS) benefit of sustained ET persistence compared with observed ET persistence. A total of 121,601 patients with HR-positive eBC were included in the analyses, of whom 29.8% was younger than 50 years at diagnosis. Younger patients had lower DFS and were more likely to discontinue ET than older patients. In patients 34 years and younger, strict ET persistence (≤30-day gaps) improved 5-year DFS proportions from 74.5% to 78.8% (4.3 percentage points [95% CI, 2.6 to 7.2]) compared with observed persistence. ET persistence strategies allowing for ≤90-day and ≤180-day gaps reduced the 5-year DFS benefit in patients 34 years and younger to 1.3 (95% CI, 0.2 to 3.7) and 1.0 (95% CI, -0.2 to 3.4) percentage points, respectively. By contrast, DFS benefits of improved ET persistence in patients after 50 years old did not exceed 1.9 percentage points, compared with observed persistence, regardless of the persistence definition. The survival benefit that could be achieved with strict ET persistence in women 34 years and younger with HR-positive eBC highlights the need for tailored strategies to improve ET persistence in this population.