Pre-Pectoral Breast Reconstruction after Mastectomy: Current Evidence, Knowledge Gaps, and Rationale for the I-PREPARE EUBREAST-11R Trial.

INTRODUCTION: Pre-pectoral implant-based breast reconstruction (IBR) has emerged as a promising alternative to conventional subpectoral approaches following nipple- or skin-sparing mastectomy. However, long-term oncological safety, complication profiles, and outcomes in specific subgroups, such as patients receiving radiation therapy (RT), remain under investigation. Contemporary evidence is mainly derived from retrospective studies with limited follow-up, reporting heterogeneous results. The I-PREPARE trial (EUBREAST-11R) was initiated by the EUBREAST (European Breast Cancer Research Association of Surgical Trialists, https://www.eubreast.org/) in order to provide high-quality data on the outcomes of pre-pectoral IBR in terms of oncological safety, complications, aesthetic results, and patient-reported outcomes, with particular attention to the impact of RT.

METHODS: The I-PREPARE trial is a prospective, international, observational cohort study assessing outcomes of IBR after therapeutic mastectomy. Adult women undergoing nipple- or skin-sparing mastectomy followed by pre-pectoral IBR (with or without synthetic/biologic mesh) are eligible. Primary endpoint is implant loss at 3 months; secondary endpoints include early and late onset complications, reoperations (≤24 months), quality of life (6, 12, and 24 months), and time to start of adjuvant treatments. Tertiary endpoints will address oncological outcomes (loco-regional recurrence, disease-free survival, breast cancer specific survival, distant-disease-free survival, overall survival, implant-associated anaplastic T-cell non-Hodgkin lymphoma). The evaluation of these endpoints will be undertaken only subject to the availability of additional dedicated funding. Data are collected via a secure eCRF and the EUBreast patient App for smartphones (https://apps.apple.com/it/app/eubreast/id6469623234; https://play.google.com/store/apps/details?id=com.brightfish.appstore.eubreast.patient&hl=it&pli=1). The study plans to enrol 1,236 patients across multiple centres and countries. The study was registered on ClinicalTrials.gov under the Trial Registration Number NCT05817175.

CONCLUSION: The I-PREPARE trial (EUBREAST-11R) aims to generate high-quality real-world evidence on the safety, efficacy, and patient-reported outcomes of pre-pectoral IBR. This initiative will address current knowledge gaps on the outcomes of pre-pectoral IBR and could help clinical decision-making for patient selection, surgical planning, and multidisciplinary care in breast reconstruction.