Background
Retrospective outcomes analysis from five National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized trials (B-15, B-16, B-18, B-22, B-25). 5,758 patients with node-positive breast cancer treated with mastectomy + adjuvant chemotherapy (±tamoxifen) and without postmastectomy radiotherapy. Analyzed to characterize locoregional failure (LRF) rates as a function of number of positive lymph nodes and tumor size, in the absence of PMRT.
Interventions and follow up
Arm A: Mastectomy + adjuvant chemotherapy (doxorubicin-based in 90%) ± tamoxifen — no postmastectomy RT
Arm B: N/A — analysis within the no-RT arm
Primary endpoint: 10-year cumulative incidence of locoregional failure (LRF) as first event, with or without distant failure
mFollow up: Median 11.1 year
Arm B: N/A — analysis within the no-RT arm
Primary endpoint: 10-year cumulative incidence of locoregional failure (LRF) as first event, with or without distant failure
mFollow up: Median 11.1 year
Results
10-year LRF (LRR ± DM) by nodal status:
1–3 positive nodes: 13.0%
4–9 positive nodes: 24.4%
≥10 positive nodes: 31.9%
Overall 10-year isolated LRF: 12.2%
Overall LRF with or without DM: 19.8%
10-year distant failure alone: 43.3%
Multivariate predictors of LRF: Number of LN+, tumor size, age, premenopausal status
1–3 positive nodes: 13.0%
4–9 positive nodes: 24.4%
≥10 positive nodes: 31.9%
Overall 10-year isolated LRF: 12.2%
Overall LRF with or without DM: 19.8%
10-year distant failure alone: 43.3%
Multivariate predictors of LRF: Number of LN+, tumor size, age, premenopausal status
Adverse events
Main adverse events: Not applicable — observational analysis, no treatment-related AEs reported. Outcomes represent natural history of LRF without PMRT.
Conclusions
In node-positive patients treated with mastectomy and adjuvant chemotherapy but without PMRT, 10-year LRF rates range from 13% (1-3 nodes) to 32% (≥10 nodes). Even in the 1-3 positive node category, a 13% LRF rate is clinically significant, supporting the consideration of PMRT. Tumor size and number of positive nodes are the dominant predictors of LRF risk.
Key Limitations
Key Limitations: Analysis limited to patients enrolled in chemotherapy trials — selection bias exists. Does not include contemporary high-risk features (e.g., TNBC, HER2+) in the risk stratification model. Older chemotherapy regimens (doxorubicin-based) may overestimate LRF risk with modern regimens including taxanes and targeted agents. LRF as "first event" underestimates total LRF because some patients develop distant metastases first (masking LRF). No RT arm available for direct comparison within these trials.
Clinical Context
This paper provided the empirical LRF risk data that underpinned the debate about PMRT in 1-3 positive node patients before the EBCTCG 2014 meta-analysis. A 13% 10-year LRF rate in the 1-3 positive node group was considered sufficiently high to justify PMRT discussions. Together with EBCTCG 2014 showing survival benefit, these data established PMRT as appropriate for all node-positive patients. The 4:1 ratio (from EBCTCG 2011) applied to these LRF rates: ~3% absolute OS benefit with PMRT in 1-3 positive node patients.
References