Omitting Radiotherapy Ups Local Recurrence Risk in Older Women With Low-Risk Breast Cancer After Breast-Conserving Surgery and Endocrine Therapy
In a phase III trial to assess whether whole-breast irradiation could be omitted in women aged ≥ 65 years with early-stage breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine treatment, Kunkler et al found increased risk of local recurrence in women not receiving radiotherapy. No significant differences between radiotherapy and no radiotherapy groups were observed for regional recurrence, distant metastases, contralateral breast cancers, new breast cancers, or overall survival. The study is reported in The Lancet Oncology.
Study Details
In the trial, 1,326 women from 76 centers in the United Kingdom, Greece, Australia, and Serbia were randomly assigned between April 2003 and December 2009 to receive radiotherapy at 40 to 50 Gy in 15 to 25 fractions (n = 658) or no radiotherapy (n = 668). Patients were considered to be at low risk of recurrence on the basis of hormone receptor–positive and axillary node-negative disease, T1 to T2 disease ≤ 3 cm at the longest dimension, and clear margins. Patients could have grade 3 tumor histology or lymphovascular invasion, but not both. The primary endpoint was ipsilateral breast tumor recurrence. Follow-up in the trial continues.
The no-radiotherapy and radiotherapy groups were generally balanced for age (median, 70 and 69 years), margins (1–5 mm in 47% and 45%, > 5 mm in 34% and 36%), tumor grade (1 in 41% and 44%, 2 in 55% and 53%, 3 in 3% and 2%), tumor side (left breast for 54% and 52%), lymphovascular invasion (5% and 4%), axillary surgery (sentinel node biopsy only in 33% and 30%, sample only in 26% and 32%, both in 16% in both), preoperative endocrine treatment (9% and 8%), and estrogen receptor status (rich in 89% and 91%).
Risk of Recurrence
After median follow-up of 5 years, ipsilateral breast tumor recurrence was observed in 26 patients (4.1%) in the no radiotherapy group vs 5 (1.3%) in the radiotherapy group (hazard ratio [HR] = 5.19, P = .0007). On multivariate analysis including pathologic tumor size, margin status, tumor grade, age, presence of lymphovascular invasion, estrogen receptor status, and use of radiotherapy, omission of radiotherapy was the only significant predictor of local recurrence (HR = 4.87, P = .0013); poor estrogen receptor status and grade 3 tumors were of borderline significance (both P = .06).
For the no radiotherapy vs radiotherapy groups, regional recurrence was observed in 1.5% vs 0.5%, distant recurrence in 1.0% vs 0.5%, contralateral breast cancer in 0.7% vs 1.5%, and new nonbreast cancer in 4.3% vs 3.7%. Five-year overall survival was 93.9% in both groups (P = .34), and 5-year breast cancer-free survival was 94.5% vs 97.6%. Among 49 patients in the no radiotherapy group and 40 in the radiotherapy group who died, 8 and 4 died from breast cancer.
Among 23 patients in the no radiotherapy group and 4 in the radiotherapy group with local recurrence who had such data available, mastectomy was performed in 12 and 2 and wide local excision occurred in 11 and 2.
The investigators concluded: “Postoperative whole-breast radiotherapy after breast-conserving surgery and adjuvant endocrine treatment resulted in a significant but modest reduction in local control for women aged 65 years or older with early breast cancer 5 years after randomisation. However, the 5-year rate of ipsilateral breast tumour recurrence is probably low enough for omission of radiotherapy to be considered for some patients.”
Ian H. Kunkler, FRCR, of Western General Hospital, Edinburgh, is the corresponding author for the Lancet Oncology article.
The study was funded by the Chief Scientist Office of the Scottish Government and Breast Cancer Institute at Western General Hospital, Edinburgh.
The authors reported no conflicts of interest.
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