Randomized trial meta-analysis reveals lower 15-year mortality from reduced recurrence in early breast cancer, indicating one death avoided per four local recurrences prevented.
Key Points
To determine whether substantial reductions in local recurrence produced by local treatments affect 15-year breast cancer mortality.
Collaborative individual patient data meta-analysis of 78 randomised treatment comparisons involving 42,000 women with early breast cancer from trials initiated by 1995.
Evaluated comparisons of radiotherapy versus no radiotherapy (n=23,500), more versus less surgery (n=9,300), and more surgery versus radiotherapy (n=9,300).
Stratified 24 local treatment comparison types by whether the 5-year local recurrence risk difference exceeded 10% (<10%, n=17,000; >10%, n=25,000).
In comparisons with >10% local recurrence difference (n=25,000), local treatment reduced 5-year local recurrence from 26% to 7% (19% absolute reduction) and 15-year breast cancer mortality from 49.5% to 44.6% (absolute reduction 5.0%, SE 0.8, 2p<0.00001).
Radiotherapy reduced 15-year breast cancer mortality after breast-conserving surgery (30.5% vs 35.9%, absolute reduction 5.4%, SE 1.7, 2p=0.0002) and after mastectomy with axillary clearance in node-positive disease (54.7% vs 60.1%, absolute reduction 5.4%, SE 1.3, 2p=0.0002).
Older radiotherapy regimens were associated with excess contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and non-breast-cancer mortality (rate ratio 1.12, SE 0.04, 2p=0.001), primarily driven by heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004).