AimIntraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. Materials and MethodsA database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) ResultsFrom 2002 to 2015, 109 patients underwent the conservative retreatment.The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. Conclusion2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.