Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial

Background Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. Methods In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours <= 4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (>= 20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m(2), methotrexate 50 mg/m(2), and fluorouracil 600 mg/m(2) every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration >= 20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. Findings Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17<middle dot>5 years (IQR 8<middle dot>4-27<middle dot>9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0<middle dot>39 [95% CI 0<middle dot>28-0<middle dot>55], p<0<middle dot>0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0<middle dot>24 [95% CI 0<middle dot>15-0<middle dot>38], p<0<middle dot>0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0<middle dot>98 [0<middle dot>54-1<middle dot>79], p=0<middle dot>95). There was no difference in overall survival between the two groups (median 18<middle dot>7 years [95% CI 16<middle dot>5-21<middle dot>5] in the no radiotherapy group vs 19<middle dot>2 years [16<middle dot>9-21<middle dot>3] in the radiotherapy group; HR 1<middle dot>08 [95% CI 0<middle dot>89-1 <middle dot>30], log-rank p=0<middle dot>43). Interpretation Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy.