BackgroundPreoperative instead of standard postoperative partial breast irradiation (PBI) after breast-conserving surgery (BCS) has the advantage of reducing the irradiated breast volume, toxicity, and number of radiotherapy sessions and can allow tumor downstaging. In this review, we assessed tumor response and clinical outcomes after preoperative PBI.Patients and MethodsWe conducted a systematic review of studies on preoperative PBI in patients with low-risk breast cancer using the databases Ovid Medline, Embase.com, Web of Science (Core Collection), and Scopus (PROSPERO registration CRD42022301435). References of eligible manuscripts were checked for other relevant manuscripts. The primary outcome measure was pathologic complete response (pCR).ResultsA total of eight prospective and one retrospective cohort study were identified (n= 359). In up to 42% of the patients, pCR was obtained and this increased after a longer interval between radiotherapy and BCS (0.5–8 months). After a maximum median follow-up of 5.0 years, three studies on external beam radiotherapy reported low local recurrence rates (0–3%) and overall survival of 97–100%. Acute toxicity consisted mainly of grade 1 skin toxicity (0–34%) and seroma (0–31%). Late toxicity was predominantly fibrosis grade 1 (46–100%) and grade 2 (10–11%). Cosmetic outcome was good to excellent in 78–100% of the patients.ConclusionsPreoperative PBI showed a higher pCR rate after a longer interval between radiotherapy and BCS. Mild late toxicity and good oncological and cosmetic outcomes were reported. In the ongoing ABLATIVE-2 trial, BCS is performed at a longer interval of 12 months after preoperative PBI aiming to achieve a higher pCR rate.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-023-13233-9.