Background
Long-term follow-up analysis (18 years) of the Danish Breast Cancer Cooperative Group (DBCG) 82b and 82c randomized trials. 3,083 patients with high-risk breast cancer (LN+ or T3/T4 or skin invasion) after mastectomy. DBCG 82b: premenopausal patients randomized to CMF ± postmastectomy RT; DBCG 82c: postmenopausal patients randomized to tamoxifen ± postmastectomy RT. RT included chest wall + regional nodes (45–50 Gy). This analysis examined the impact of RT on the pattern of disease recurrence over 18 years.
Interventions and follow up
Arm A: CMF (82b) or tamoxifen (82c) + postmastectomy RT (45–50 Gy to CW + regional nodes)
Arm B: CMF (82b) or tamoxifen (82c) alone (no RT)
Primary endpoint: 18-year locoregional recurrence (LRR) and distant metastasis (DM) as first event
mFollow up: Median potential follow-up 18 year
Arm B: CMF (82b) or tamoxifen (82c) alone (no RT)
Primary endpoint: 18-year locoregional recurrence (LRR) and distant metastasis (DM) as first event
mFollow up: Median potential follow-up 18 year
Results
18-year LRR as first event: 14% (RT) vs 49% (no RT), RR 0.23 (95% CI 0.19–0.27), P<.001
18-year DM following LRR: 6% (RT) vs 35% (no RT), P<.001
18-year any DM: 53% (RT) vs 64% (no RT), RR 0.78 (95% CI 0.71–0.86), P<.001
18-year any breast cancer event: 59% (RT) vs 73% (no RT), RR 0.68 (95% CI 0.63–0.75), P<.001
18-year DM following LRR: 6% (RT) vs 35% (no RT), P<.001
18-year any DM: 53% (RT) vs 64% (no RT), RR 0.78 (95% CI 0.71–0.86), P<.001
18-year any breast cancer event: 59% (RT) vs 73% (no RT), RR 0.68 (95% CI 0.63–0.75), P<.001
Adverse events
Main adverse events: RT was associated with higher rates of cardiac mortality at shorter follow-up in earlier reports (left-sided RT with older technique); with 18-year follow-up, cardiac toxicity was an acknowledged limitation of the older RT technique used. Modern RT with cardiac-sparing techniques substantially mitigates this risk.
Conclusions
Postmastectomy RT changes the long-term disease recurrence pattern in high-risk breast cancer: it reduces LRR from 49% to 14% at 18 years, and through prevention of LRR-to-DM progression, reduces the rate of subsequent distant metastasis. This analysis provides the long-term mechanistic evidence that PMRT reduces breast cancer mortality by preventing LRR-driven distant spread.
Key Limitations
Key Limitations: Used CMF chemotherapy (not anthracycline/taxane-based regimens); the proportional benefit of PMRT in the context of modern systemic therapy may differ. Older RT techniques with higher cardiac doses than current practice. High baseline LRR rates (49% without RT) reflect a high-risk population; results may overestimate benefit relative to modern lower-risk cohorts receiving more effective systemic therapy. The 82b/82c original trials were criticized for potentially suboptimal ALND extent, leading to higher LRR rates in the no-RT arm.
Clinical Context
Together with the British Columbia RCT (Ragaz et al), the Danish DBCG 82b/82c trials provided the first randomized evidence that postmastectomy RT improves breast cancer survival, not merely local control. These trials catalyzed the modern PMRT era and the subsequent EBCTCG meta-analyses. For high-risk patients (≥4 positive nodes, T3/T4), PMRT is now standard of care across all major guidelines.
References