Update on Accelerated Whole Breast Irradiation

Published:January 26, 2023DOI:


      Since the advent of breast conservation, adjuvant radiation therapy (RT) has been standard of care following breast conserving surgery (BCS). Radiation therapy following BCS has traditionally been whole breast irradiation (WBI); studies comparing breast conservation to mastectomy utilized standard fractionation WBI, which delivers treatment daily over 5 to 7 weeks (1.8-2 Gy/fraction) and was the standard for decades. More recently, multiple randomized trials have compared standard fractionation WBI to moderately hypofractionated WBI (2.66 Gy/fraction, 15-16 fractions), which allows for completion of treatment in 3 to 4 weeks. Results have demonstrated no difference in local control between these two approaches with comparable toxicity and cosmetic outcomes with long-term follow-up. As such, moderately hypofractionated WBI represents the standard of care approach for most patients with early-stage breast cancer following BCS at this time. In the past few years, ultra-hypofractionated WBI (5.2-5.7 Gy/fraction, 5 fractions) has emerged with promising outcomes; 5-year outcomes from the FAST-Forward randomized trial demonstrated noninferiority between ultra-hypofractionated WBI and moderately hypofractionated WBI. Moving forward, long-term outcomes from ultra-hypofractionated WBI studies are expected, as well as the potential for incorporating moderately hypofractionated regimens into patients requiring regional nodal irradiation following BCS. Finally, the advent of ultra-short regimens may allow clinicians to re-evaluate treatment de-intensification in early-stage breast cancer to consider radiation therapy alone following BCS in lieu of endocrine therapy.


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        • Fisher B
        • Anderson S
        • Bryant J
        • et al.
        Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
        N Engl J Med. 2002; 347: 1233-1241
        • Veronesi U
        • Cascinelli N
        • Mariani L
        • et al.
        Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer.
        N Engl J Med. 2002; 347: 1227-1232
        • Darby S
        • McGale P
        • Correa C
        • et al.
        Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials.
        Lancet. 2011; 378: 1707-1716
        • Ma AM
        • Barone J
        • Wallis AE
        • et al.
        Noncompliance with adjuvant radiation, chemotherapy, or hormonal therapy in breast cancer patients.
        Am J Surg. 2008; 196: 500-504
        • Shah C
        • Keisch M
        • Khan A
        • et al.
        Ultra-short fraction schedules as part of de-intensification strategies for early-stage breast cancer.
        Ann Surg Oncol. 2021; 28: 5005-5014
        • Yarnold J
        • Ashton A
        • Bliss J
        • et al.
        Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial.
        Radiother Oncol. 2005; 75: 9-17
        • Owen JR
        • Ashton A
        • Bliss JM
        • et al.
        Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial.
        Lancet Oncol. 2006; 7: 467-471
        • Bentzen SM
        • Agrawal RK
        • Aird EGA
        • et al.
        The UK Standardisation of Breast Radiotherapy (START) trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.
        Lancet Oncol. 2008; 9: 331-341
        • Haviland JS
        • Owen JR
        • Dewar JA
        • et al.
        The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of earl breast cancer: 10-year follow-up results of two randomized controlled trials.
        Lancet Oncol. 2013; 14: 1086-1094
        • Haviland JS
        • Mannino M
        • Griffin C
        • et al.
        Late normal tissue effects in the arm and shoulder following lymphatic radiotherapy: results from the UK START (Standardisation of Breast Radiotherapy) trials.
        Radiother Oncol. 2018; 126: 155-162
        • Whelan TJ
        • Pignol JP
        • Levine MN
        • et al.
        Long-term results of hypofractionated radiation therapy for breast cancer.
        N Engl J Med. 2010; 362: 513-520
        • Shaitelman SF
        • Lei X
        • Thompson A
        • et al.
        Three-year outcomes with hypofractionated versus conventionally fractionated whole-breast irradiation: results of a randomized, noninferiority clinical trial.
        J Clin Oncol. 2018; 36JC1800317
        • Weng JK
        • Lei X
        • Schlembach P
        • et al.
        Five-year longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.
        Int J Radiat Oncol Biol Phys. 2021; 111: 360-370
        • Smith BD
        • Bellon JR
        • Blitzblau R
        • et al.
        Radiation therapy for the whole breast: executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline.
        Pract Radiat Oncol. 2018; 8: 145-152
        • Brunt AM
        • Haviland JS
        • Sydenham M
        • et al.
        Ten-year results of FAST: a randomized controlled trial of 5-fraction whole-breast radiotherapy for early breast cancer.
        J Clin Oncol. 2020; 38: 3261-3272
        • Eldredge-Hindy H
        • Pan J
        • Rai SN
        • et al.
        A Phase II Trial of once weekly hypofractionated breast irradiation for early stage breast cancer.
        Ann Surg Oncol. 2021; 28: 5880-5892
        • Dragun AE
        • Ajkay NJ
        • Riley EC
        • et al.
        First results of a phase 2 trial of once-weekly hypofractionated breast irradiation (WHBI) for early-stage breast cancer.
        Int J Radiat Oncol Biol Phys. 2017; 98: 595-602
        • Dragun AE
        • Quillo AR
        • Riley EC
        • et al.
        A phase 2 trial of once-weekly hypofractionated breast irradiation: first report of acute toxicity, feasibility, and patient satisfaction.
        Int J Radiat Oncol Biol Phys. 2013; 85: e123-e128
        • Eldredge-Hindy H
        • Gaskins J
        • Dragun A
        • et al.
        Patient-reported outcomes and cosmesis after once-weekly hypofractionated breast irradiation in medically underserved patients.
        Int J Radiat Oncol Biol Phys. 2020; 107: 934-942
        • Murray Brunt A
        • Haviland JS
        • Wheatley DA
        • et al.
        Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.
        Lancet. 2020; 395: 1613-1626
        • Meattini I
        • Becherini C
        • Boersma L
        • et al.
        European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.
        Lancet Oncol. 2022; 23: e21-e31
        • Vicini F
        • Winter K
        • Freedman GM
        • et al.
        NRG RTOG 1005: A Phase III trial of hypofractionated whole breast irradiation with concurrent boost vs. conventional whole breast irradiation plus sequential boost following lumpectomy for high risk early-stage breast cancer.
        Int J Radiat Oncol Biol Phys. 2022; 114: S1
        • Chakraborty S
        • Chatterjee S.
        HYPORT adjuvant acute toxicity and patient dosimetry quality assurance results: interim analysis.
        Radiother Oncol. 2022; 174: 59-68
        • Wang SL
        • Fang H
        • Song YW
        • et al.
        Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.
        Lancet Oncol. 2019; 20: 352-360
      1. FAST-Forward: guidelines to outlining, planning, and delivery of lymphatic radiotherapy for Fast-Forward trial patients. Available at:

        • Buszek SM
        • Liny HY
        • Bedrosian I
        • et al.
        Lumpectomy plus hormone or radiation therapy alone for women aged 70 years or older with hormone receptor-positive early stage breast cancer in the modern era: an analysis of the National Cancer Database.
        Int J Radiat Oncol Biol Phys. 2019; 105: 795-802
        • Naoum GE
        • Taghian A.
        Endocrine treatment for 5 years or radiation for 5 days for patients with early breast cancer older than 65 years: can we do it right? [e-pub ahead of print].
        J Clin Oncol. 2022;
        • Ward MC
        • Vicini F
        • Al-Hilli Z
        • et al.
        Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.
        Int J Radiat Oncol Phys. 2020; 182: 355-365
        • Ward MC
        • Vicini F
        • Chadha M
        • et al.
        Radiation therapy without hormone therapy for women age 70 or above with low-risk early breast cancer: a microsimulation.
        Int J Radiat Oncol Phys. 2019; 105: 296-306
      2. Exclusive endocrine therapy or partial breast irradiation for women aged ≥ 70 years early stage breast cancer (EUROPA). Available at:

      3. De-escalation of breast radiation trial for hormone sensitive, HER-2 negative, oncotype recurrence score less than or equal to 18 breast cancer (DEBRA). Available at: