Background
Randomized controlled trial (British Columbia RCT). 318 premenopausal women with lymph node-positive breast cancer after modified radical mastectomy (MRMX) and CMF adjuvant chemotherapy. Randomized to CMF alone vs CMF + locoregional RT (37.5 Gy in 16 fractions over 3.3 weeks, to the chest wall and regional nodes). This report presents the 20-year outcomes of the trial.
Interventions and follow up
Arm A: CMF chemotherapy + locoregional RT (37.5 Gy in 16 fractions)
Arm B: CMF chemotherapy alone
Primary endpoint: Overall survival, locoregional recurrence-free survival
mFollow up: Median 249 months (live patients)
Arm B: CMF chemotherapy alone
Primary endpoint: Overall survival, locoregional recurrence-free survival
mFollow up: Median 249 months (live patients)
Results
20-year OS: 47% (CMF+RT) vs 37% (CMF alone), RR 0.73 (95% CI 0.55–0.98), P=.03
20-year locoregional recurrence-free survival: 90% (CMF+RT) vs 74% (CMF alone), RR 0.36 (95% CI 0.18–0.71), P=.002
20-year systemic relapse-free survival: 48% vs 31%, RR 0.66 (95% CI 0.49–0.88), P=.004
20-year breast cancer-free survival: 48% vs 30%, RR 0.63 (95% CI 0.47–0.83), P=.001
20-year locoregional recurrence-free survival: 90% (CMF+RT) vs 74% (CMF alone), RR 0.36 (95% CI 0.18–0.71), P=.002
20-year systemic relapse-free survival: 48% vs 31%, RR 0.66 (95% CI 0.49–0.88), P=.004
20-year breast cancer-free survival: 48% vs 30%, RR 0.63 (95% CI 0.47–0.83), P=.001
Adverse events
Main adverse events: RT was delivered using older techniques; cardiac mortality was 1.8% (CMF+RT) vs 0.6% (CMF alone), a small but notable excess. Modern cardiac-sparing RT techniques substantially reduce this risk. No excess in non-cardiac non-breast cancer deaths.
Conclusions
At 20-year follow-up, postmastectomy locoregional RT (37.5 Gy/16 fx) added to CMF chemotherapy significantly improved all cancer endpoints, including overall survival (47% vs 37%, P=.03). This is one of two landmark randomized trials (along with the Danish DBCG 82b/82c) demonstrating that PMRT improves breast cancer survival, not merely locoregional control.
Key Limitations
Key Limitations: Small trial (318 patients), single institution. CMF is no longer the standard systemic regimen — modern anthracycline/taxane-based chemotherapy reduces locoregional recurrence more than CMF, potentially reducing the absolute benefit of RT. All patients were lymph node-positive (primarily high-risk); benefit in 1-3 positive node patients was extrapolated from these data rather than directly shown. The RT schedule (37.5 Gy/16 fx) predates current standard technique; cardiac doses were higher than modern practice.
Clinical Context
The British Columbia trial and Danish trials formed the evidence base for the 2001 EBCTCG meta-analysis that confirmed PMRT survival benefit. The EBCTCG 2014 meta-analysis (Lancet) subsequently demonstrated specific survival benefit in the 1-3 positive node subgroup, completing the evidence base for PMRT across all nodal categories. These trials established that local control translates into survival benefit through prevention of subsequent distant metastasis.
References