Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer

Abstract

Purpose: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented.

Methods: Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens.

Results: A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred.

Conclusion: At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

Trial registration: ClinicalTrials.gov NCT00107497.

Conflict of interest statement

Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

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Adrian Murray Brunt

Consulting or Advisory Role: Roche, Genomic Health

Speakers' Bureau: Roche, BMS, Novartis, Genomic health

Research Funding: Roche (Inst), Novartis (Inst)

Peter Barrett-Lee

Expert Testimony: Roche/Genentech

Andy Goodman

Honoraria: Genomic Health, Bristol Myers Squibb

Adrian Harnett

Honoraria: Genomic Health

Consulting or Advisory Role: General Medical Council, UK

Travel, Accommodations, Expenses: James Paget University Hospital

Martin Hogg

Honoraria: Clovis, Pfizer

Isabel Syndikus

Travel, Accommodations, Expenses: Bayer

Duncan Wheatley

Honoraria: AstraZeneca, Roche, Pfizer, Lilly

Consulting or Advisory Role: Roche, Pfizer, AstraZeneca, Novartis, Daiichi Sankyo

Travel, Accommodations, Expenses: Roche, Lilly

Judith M. Bliss

Research Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Medivation (Inst), Puma Biotechnology (Inst), Clovis Oncology (Inst), Pfizer (Inst), Janssen-Cilag (Inst), Roche (Inst), Novartis (previously GSK) (Inst)

Travel, Accommodations, Expenses: Pfizer

No other potential conflicts of interest were reported.

Figures

FIG 1.

Physician assessments of late normal tissue effects. (A) Breast shrinkage to 10 years; (B) time to first reported moderate/marked breast shrinkage; (C) breast induration to 10 years; (D) time to first reported moderate/marked breast induration; (E) breast edema to 10 years; (F) time to first reported moderate/marked breast edema; (G) telangiectasia to 10 years; and (H) time to first reported moderate/marked telangiectasia.

FIG 1.

Physician assessments of late normal tissue effects. (A) Breast shrinkage to 10 years; (B) time to first reported moderate/marked breast shrinkage; (C) breast induration to 10 years; (D) time to first reported moderate/marked breast induration; (E) breast edema to 10 years; (F) time to first reported moderate/marked breast edema; (G) telangiectasia to 10 years; and (H) time to first reported moderate/marked telangiectasia.

FIG A1.

Examples of no change and marked change in photographic breast appearance.

FIG A2.

FAST Trial profile. FU, follow-up; fr, fraction; RT, radiotherapy; trt, treatment. (*) Only major treatment deviations are listed. Minor deviations due to public holidays, machine service days, and machine breakdowns not included.