Frontiers and future directions in radiotherapy for breast cancer: considerations of net clinical benefit

Breast cancer radiotherapy is simultaneously undergoing a triple transformation: treatment de-escalation, technical refinement, and multidisciplinary collaboration. Two seemingly contradictory development paths have emerged in the field: treatment de-escalation and equipment/technology upgrading.-Taking clinical net benefit as the core evaluation principle, this article systematically reviews cuttingedge advances in the field and puts forward the following core viewpoints. First, in photon radiotherapy, regimens such as 26 Gy in 5 fractions for breast or chest wall irradiation and 40 Gy in 15 fractions for regional nodal irradiation have obtained sufficient evidence-based support; the core criterion for omitting radiotherapy is not merely identifying patients at low risk of recurrence, but rather demonstrating that the absolute benefit of radiotherapy is so marginal that patients are willing to forgo it. Second, proton therapy can be adopted after confirming the absolute benefit threshold through dual-plan comparison, whereas carbon ion therapy, boron neutron capture therapy, and FLASH radiotherapy remain insufficiently mature and cannot directly replace established photon therapy. Third, the combination of HER2-directed antibody-drug conjugates, CDK4/6 inhibitors, and immunotherapy with radiotherapy can be implemented in limited clinical scenarios; however, short-term feasibility does not equate to long-term safety, retrospective associations do not equate to causality, and local efficacy does not equate to synergistic enhancement. Fourth, breast cancer radiotherapy in the future will not evolve along a single technology substitution route, but will develop into a complete clinical system of tiered decision-making. This article establishes a tiered decision-making framework for breast cancer radiotherapy centered on clinical net benefit, clarifies the applicable boundaries and evidence gaps of various technologies, and provides a practical reference for the homogenized promotion of breast radiotherapy.