Efficacy and safety of hypofractionated versus conventional radiotherapy in breast cancer: a systematic review and meta-analysis

Background Breast cancer is one of the most frequent cancers globally, and radiotherapy plays an important key role in reducing the chance of recurrence following breast-conserving surgery. As an alternative to traditional fractionated radiotherapy (CFRT), hypofractionated whole-breast irradiation (HFRT) has gained popularity since it provides similar oncological results over shorter treatment periods. Nevertheless, the comparative effectiveness and safety profile of hypofractionated versus conventional fractionation schedules remains an area of ongoing evaluation. Aim To compare the efficacy and safety of HFRT versus CFRT in patients with breast cancer, with particular emphasis on disease-free survival and treatment-related toxicity. Methods A comprehensive search of PubMed, Cochrane Library, Scopus, Web of Science, and Embase was conducted through December 2024. Randomized controlled trials (RCTs) and comparative studies evaluating HFRT versus CFRT in early-stage breast cancer. Key outcomes assessed included disease-free survival (DFS) and treatment-related toxicities, particularly lymphedema and acute radiation dermatitis. The Mantel–Haenszel method to calculate risk ratios (RRs) with 95% confidence intervals (CI) was used. Results Eight studies comprising 5,495 breast cancer patients were identified. The meta-analysis demonstrated no significant differences in disease-free survival (DFS) in 5 years ( RR = 1.01, 95% CI 0.96–1.06; P = 0.83 ). Similarly, no significant difference was observed in the incidence of lymphedema between HFRT and CFRT (RR = 1.19, 95% CI 0.94–1.51; P = 0.15). Regarding acute radiation dermatitis, a statistically significant difference favoring HFRT was observed under the fixed-effects model (RR = 1.62, 95% CI 1.20–2.18; P = 0.002). However, due to substantial heterogeneity across studies (I² = 90%), a random-effects model was applied, which demonstrated no statistically significant difference between treatment groups (RR = 1.43, 95% CI 0.51–4.01; P = 0.50). These results should be interpreted with caution given the high between-study variability. Conclusion HFRT demonstrated comparable oncological outcomes to CFRT, with a trend toward reduced acute skin toxicity, indicating that it could be a promising therapy option for early-stage breast cancer. Standardizing radiation treatments and evaluating long-term toxicity and patient-reported results should be the goals of future research. Also, the observed variability across studies warrants cautious interpretation of the pooled estimates, particularly for outcomes demonstrating substantial heterogeneity. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42025631012.