Current evidence and future directions of ultra-accelerated regimens in breast cancer

Multiple large randomized trials have confirmed the safety and efficacy of ultrahypofractionation in early-stage breast cancer. For accelerated partial breast irradiation (APBI), the external beam regimen of 30 Gy in 5 fractions delivered once daily, as well as brachytherapy, has demonstrated superior toxicity profiles compared to whole breast irradiation (WBI) without compromising tumor control in low-risk patients. In addition, the FAST and FAST-Forward trials showed non-inferiority of 5-fraction regimens for WBI compared to conventional or moderate hypofractionation. Emerging data also suggest feasibility of ultrahypofractionation in regional nodal irradiation (RNI) and postmastectomy radiation therapy (PMRT), with promising results from the FAST-Forward nodal substudy and HYPART trial. However, long-term data remain limited in these higher-risk populations. This review aims to critically evaluate current evidence supporting ultrahypofractionated radiotherapy in breast cancer and assess its readiness for routine clinical implementation across various clinical scenarios, including APBI, WBI, RNI, and PMRT. Ultrahypofractionation has established itself as a viable standard for selected patients undergoing APBI or WBI, particularly in low-risk early-stage breast cancer. While early results in RNI and PMRT settings are encouraging, routine implementation remains premature without mature efficacy and toxicity data. Careful patient selection and protocol adherence are essential. Ongoing prospective trials are expected to expand indications and guide optimal practice in the future. Not applicable.