Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed. 15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries. The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. Four randomised trials testing fraction sizes in the range 2.7–3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues.

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