Background
Phase III, randomized non-inferiority trial. 2215 patients with early breast cancer (pT1-3a pN0-1 M0) after BCS (95%) or mastectomy, including regional nodal RT per protocol. UK multicenter START-B trial compared moderately hypofractionated whole-breast RT (40Gy/15f/3 weeks) with standard fractionation (50Gy/25f/5 weeks). Based on radiobiological modeling suggesting breast cancer has a low α/β ratio (~4 Gy), predicting equivalent or superior tumor control with hypofractionation.
Interventions and follow up
Arm A: 40Gy in 15 fractions over 3 weeks (hypofractionated)
Arm B: 50Gy in 25 fractions over 5 weeks (conventional fractionation)
Primary endpoint: Local-regional tumor relapse (non-inferiority) and normal tissue effects
mFollow up: 10 years
Arm B: 50Gy in 25 fractions over 5 weeks (conventional fractionation)
Primary endpoint: Local-regional tumor relapse (non-inferiority) and normal tissue effects
mFollow up: 10 years
Results
10-yr local relapse: 4.3% vs 5.5% (40Gy vs 50Gy), HR 0.77, 95% CI 0.51–1.16 — non-inferior
10-yr OS: 80.8% vs 78.2%, HR 0.85, 95% CI 0.69–1.04
Breast induration (10-yr): 9.5% (40Gy) vs 15.7% (50Gy) — significantly less fibrosis with hypofractionation
10-yr OS: 80.8% vs 78.2%, HR 0.85, 95% CI 0.69–1.04
Breast induration (10-yr): 9.5% (40Gy) vs 15.7% (50Gy) — significantly less fibrosis with hypofractionation
Adverse events
Cosmetic/fibrosis: Photographic breast appearance change 38.0% vs 47.1% (40Gy vs 50Gy) at 10 years; breast induration significantly lower with 40Gy.
Other late effects: Breast edema and telangiectasia similar; ischemic heart disease and contralateral breast cancer rates similar between arms.
Other late effects: Breast edema and telangiectasia similar; ischemic heart disease and contralateral breast cancer rates similar between arms.
Conclusions
40Gy in 15 fractions was non-inferior to 50Gy in 25 fractions for local tumor control and produced significantly less late breast toxicity (induration, cosmetic change). START-B established hypofractionation as the standard of care for whole-breast RT in early breast cancer globally.
Key Limitations
Most patients had early-stage, node-negative disease at enrollment — extrapolation to node-positive, larger-tumor patients receiving regional nodal irradiation requires care. The START-B schedule was tested predominantly post-BCS; data in mastectomy patients are less robust. Only approximately 40% of patients received systemic therapy, limiting interpretation in the modern era of intensive systemic treatment. The 40Gy/15f schedule differs from the FAST-Forward regimen (26Gy/5f/1 week) which has since emerged as an ultra-hypofractionation option.
Clinical Context
START-B transformed breast radiation practice globally — 40Gy/15f has become the most widely used adjuvant RT schedule in early breast cancer in the UK, Europe, and increasingly worldwide. ESMO, ASTRO, and NICE guidelines endorse this schedule as preferred. The FAST-Forward trial (2020) subsequently demonstrated non-inferiority of 26Gy/5f/1 week, offering further convenience. Together, these trials have established hypofractionation as the standard rather than the exception in early breast cancer RT.