The impact of isolated local recurrence on long-term outcome in early-breast cancer patients after breast-conserving therapy

Purpose: To analyse the prognostic impact of isolated local recurrence (ILR) on longterm outcome for early-breast cancer patients treated with breast-conserving therapy. Material and methods: The data of the EORTC 22881-10882 'boost-no boost' and 22922-10925 'IM-MS' trials were used to analyse the prevalence and outcome following ILR. A multistate model described the impact of intermediate events on long-term outcomes, taking into account various prognostic factors. This model was used to predict long-term outcomes after ILR. Results: Of the 8367 patients included, 726 experienced an ILR, 11.6% of them within the first 2 years and 30.0% after 10 years. Ten-year cumulative breast cancer mortality rates after ILR were 58.2% in patients with an ILR within 2 years, 31.0% for ILR between 2 and 4 years, 17.6% in patients with an ILR between 4 and 10 years, and 29.7% for ILR after year 10 (p < 0.001). The multistate model showed that when tumour-free, younger breast cancer patients had a higher probability of developing ILR compared to older patients. Shorter time to ILR was associated with a higher chance to develop distant metastases (DM), and a shorter time to development of DM were associated with an increased hazard of breast cancer-related death. The multistate model enabled prediction of long-term outcome based on individual patient covariates, length of follow-up without recurrence and timing of ILR since randomisation. Conclusions: Outcome of early-breast cancer changed not only according to baseline risk factors but also according to the presence of intermediate events, time to these events, and subsequent followup without any further events. (c) 2021 Elsevier Ltd. All rights reserved.