The Critical Role of Dose Homogeneity in Modern Breast Hypofractionation

The evolution of breast cancer radiation therapy has witnessed a paradigm shift from conventional fractionation to hypofractionation and now ultrahypofractionation, with multiple randomized trials demonstrating noninferiority in both disease control and cosmetic outcomes. A central, yet underemphasized, determinant of this success is plan optimization by dose homogeneity. As fraction size increases, the biological impact of dose heterogeneity becomes magnified, making volumetric control of high-dose regions essential for both cosmesis and reducing late effects. This comprehensive review traces the progression from 2-dimensional central axis prescriptions to 3-dimensional volumetric optimization, examining how technological advances have enabled safe delivery of larger fraction sizes, partially through the ability to improve dose homogeneity. Dosimetric parameters across landmark trials have shown the importance of dose homogeneity, and metrics such as V105% <5% to 10%, V107% <2%, and maximum dose <110% are critical for successful hypofractionation. The evidence reveals that breast size, not fractionation schedule, drives cosmetic risk when homogeneity is optimized. We provide practical recommendations for achieving these standards using modern planning techniques, emphasizing that dose homogeneity must be considered a fundamental requirement, not a secondary endpoint, in contemporary breast radiation therapy.