Introduction
breast cancer
RECURRENCES, EVENTS, RECURRENCE, BREAST CANCER
Despite meaningful incremental improvements in screening, local treatment and adjuvant therapies, including endocrine therapies (AETs), estrogen receptor (ER)-positive breast cancer (BC) remains associated with a significant long-term risk of late relapse. Recommendations for extended AETs after 5 years are evolving due to recently published trials results: in patients at intermediate and high risk of recurrence, current guidelines recommend 7 to 10 years of adjuvant endocrine therapy, including at least 5 years of aromatase inhibitors (AI) given either upfront or as part of an early switch strategy after 2–3 years of tamoxifen [Suboptimal adherence to endocrine therapy can affect BC outcomes as soon as the patients become non-adherent. We previously showed that biochemical non-adherence to tamoxifen over the first year was associated with an absolute 5.9% increase in the risk of distant recurrences at 3 years [Although the prognostic relevance of adherence is well established, survival outcomes in most trials are analyzed according to the intention-to-treat (ITT) principle, which means that all patients who were enrolled in the trial are included in the analyses and are analyzed according to their randomized treatment assignment. Where there is considerable non-adherence to assigned treatment and late survival events, a frequent situation in trials with long-term follow-up, the on-treatment effect may be underestimated [These recent techniques are structural methods, relying on counterfactual survival times (i.e. survival times that would have been observed in the absence of non-adherence [