The breast hypofx trials were designed to be isoequivalent for 1) tumor control, and 2) late effects. Here is an excerpt from the UK START trialists introduction section:Normal and malignant tissues vary in their responses to radiotherapy fraction size, termed fractionation sensitivity. Responses ar...

It’s a function of EQ2 dose. 40 in 15 is closer to 45 Gy in comparison to 50 Gy with conventional fractionation which leads to both less acute and chronic effects (less total dose). 

The Oxford group (and others I'm sure) often talk about this in terms of a/b ratio. As breast tumors and surrounding normal tissues have a similar, relatively low a/b ratio which leads to hypofractionation giving similar cure rates with lower normal tissue dose. Just one of many articles on thi...

Total dose, dose/fraction, AND total time contribute to the timing and severity of the skin reactions. If you treat hypo-fractionation 5 days a week, you are driving more dose per week into the skin (1325 cGy/week vs 1000 cGy/week). Despite that, the skin reactions are less, which as above is no do...