ArticlesBreast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial
Introduction
Breast cancer is a growing global health care issue in older women. The incidence of breast cancer has risen steadily in most European countries between 1990 and 2002 in women aged 70 years or older.1 In several clinical trials, low-risk patients have been identified in whom the effect of postoperative whole-breast irradiation is modest,2, 3, 4 although these studies have been done mainly in younger patient populations. However, in older patients, the biology of breast cancer might be less aggressive, in view of the increased proportion of hormone receptor-positive tumours in this age group.
Postoperative whole-breast radiotherapy remains the standard of care for most patients treated by breast-conserving surgery, irrespective of age and other risk factors.5 However, little evidence exists for the role of postoperative radiotherapy in older patients after breast-conserving surgery and adjuvant endocrine treatment because many trials, historically, excluded patients older than age 70 years. Extrapolation of the results of trials in younger patients to older patients might not be valid, particularly because of the competing risks of comorbidities in older patients. Data for the effect of age on local recurrence after breast-conserving surgery have been conflicting. In some trials, ipsilateral breast tumour recurrence falls with increasing age6 or no effect is seen.7, 8 However, patients older than 65 years (and particularly those older than 75 years) were not well represented in any of these trials. Since tamoxifen with or without9, 10 adjuvant radiotherapy reduces the risk of tumour recurrence, we designed a randomised controlled trial in a group of older, low-risk, node-negative women with invasive breast cancer after breast-conserving surgery and adjuvant endocrine treatment to assess the effect omission of whole-breast irradiation has on local control.
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Participants
We did a phase 3 randomised controlled trial at 76 specialist cancer centres and district or regional hospitals in four countries (the UK, Greece, Australia, and Serbia; appendix pp 5–6). We recruited women aged 65 years or older with breast cancer who had undergone breast-conserving surgery and pathological axillary staging (ipsilateral four-node lower axillary node sample, sentinel node biopsy, or axillary node clearance). Eligibility criteria were: T1–T2 (up to 3 cm, longest dimension); N0;
Results
Between April 16, 2003, and Dec 22, 2009, 1326 patients were randomly allocated to either no radiotherapy (n=668) or whole-breast radiotherapy (n=658; figure 1). Of these, 39 did not receive radiotherapy after randomisation and five received radiotherapy when they had been randomly allocated to the no radiotherapy group. Another three patients did not begin endocrine treatment after randomisation or stopped taking it shortly after starting. 1263 patients were recruited from the UK, 22 were from
Discussion
The null hypothesis of the PRIME II study was that there was no difference between the radiotherapy and no radiotherapy groups in terms of local recurrence at 5 years, with an alternative hypothesis of a 3% difference between groups (2% with radiotherapy vs 5% with no radiotherapy). On the basis of the results of this trial, we can reject the null hypothesis (p=0·0002, log-rank test). At median follow-up of 5 years, the absolute risk reduction in ipsilateral breast tumour recurrence at 5 years
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