PMRT selection in T1-T2, 1-3 node-positive breast cancer
ForpT1-T2, 1-3 N+ breast after mastectomy + ALND, no PMRT
TL;DR10y KM LRR±SDR 15.9% without PMRT in pT1-T2 1-3 N+; age <45 with >25% nodes positive reached 58.0%.
Clavicular nodes carried 19 of 57 regional recurrences (33%) versus 2 for internal mammary, so the residual risk this model flags sits mostly in the axillary-supraclavicular field. In women ≥45 with ≤25% nodes positive, 10y LRR±SDR was 10.8%, near the authors' <10% omission threshold, while medial or ER-negative tumors pushed that subset to approximately 20%.
In a woman ≥45 with a lateral, ER-positive pT1-T2 tumor and ≤25% of ALND nodes positive, this supports discussing PMRT omission; it does not extend to SLNB-only staging, where the nodal-ratio factor cannot be computed.
Clavicular nodes carried 19 of 57 regional recurrences (33%) versus 2 for internal mammary, pointing PMRT coverage at the supraclavicular field. Age <45, >25% nodes positive, medial location and ER-negative status each moved 10y LRR above 20%, giving a factor-based frame for the 1-3 N+ PMRT discussion.
11 details
Retrospective population-based cohort from the BCCA Breast Cancer Outcomes Unit database. N=821 of 1117 identified, after excluding 296 who received RT. Cox multivariable modeling, then a classification model built from the significant factors. Median follow-up 7.7y.
pT1-T2, 1-3 positive axillary nodes, diagnosed 1989-1997, all treated with modified radical mastectomy and axillary dissection. Excluded pT3-T4, ≥4 N+, M1 and unknown pTN. Median age 62.
Adjuvant systemic therapy in 94% per BCCA guidelines: chemo alone 21.7%, hormonal alone 57.1%, both 15.1%. Chemo was AC, CMF or FAC; hormonal therapy was mostly tamoxifen.
No pt received locoregional RT; the study defines baseline no-PMRT risk to inform selection, not RT efficacy. Authors anchor benefit estimates on an RT relative LRR reduction of approximately two-thirds.
Primary: isolated LRR (chest wall, axillary, infraclavicular, IMN as first site) and LRR±simultaneous distant recurrence. Secondary: BCSS and OS.
Overall 10y LRR±SDR 15.9%. Each of age <45, T2, grade 3, ER-negative, medial location, >1 N+ or >25% N+ alone conferred >20% 10y LRR on univariate analysis. Age was the first model split (29.3% vs 13.7%, p<0.0001).
| Factor | ILRR HR (95% CI), p | LRR±SDR HR (95% CI), p |
|---|---|---|
| Age <45 vs ≥45 | 3.44 (1.68-7.07), p=0.001 | 3.22 (1.54-6.75), p=0.002 |
| >25% vs ≤25% nodes positive | 2.00 (0.99-4.05), p=0.05 | 2.61 (1.31-5.22), p=0.006 |
| Medial vs lateral | 2.46 (1.15-5.26), p=0.002 | 3.69 (2.17-6.29), p=0.0001 |
| ER-negative vs positive | 2.02 (1.16-3.54), p=0.01 | 1.82 (1.05-3.17), p=0.03 |
| Subgroup | N | ILRR | LRR±SDR |
|---|---|---|---|
| Age <45, >25% N+ | 19 | 47.6% | 58.0% |
| Age <45, ≤25% N+ | 104 | 18.5% | 23.8% |
| Age ≥45, >25% N+ | 122 | 20.6% | 26.7% |
| Age ≥45, ≤25% N+ | 570 | 8.7% | 10.8% |
No-PMRT LRR here (13-16% at 10y) sits well below the ~30% in DBCG 82b/82c and nearer the BCCA randomized trial (16% at 10y) and systemic-therapy trial cohorts (12-20%). Authors attribute the gap to axillary staging, systemic therapy and selection differences.
Excluding the 296 PMRT recipients likely removed higher-risk pts, biasing baseline risk downward. The >25% nodes positive ratio depends on ALND node yield, and its ILRR HR CI (0.99-4.05) touches 1. The ER status row in Table 1 shows a transposition in the source.
Authors propose <10% 10y LRR as a low-risk group that may be spared PMRT, >30% as justifying it, and 15-20% as the threshold for discussion. The model supports considering PMRT in all women <45 and recommending it when >25% of nodes are positive.
Retrospective single-province no-RT cohort; excluded PMRT recipients; data-driven breakpoints, no validation set; pre-taxane, ALND-era systemic therapy limits transfer to modern pts.
- Does the risk model validate with modern systemic therapy?
- Nodal-ratio factor usable after SLNB-only axillary staging?
- Do genomic risk scores refine PMRT selection in 1-3 N+?
📚 Sources · 📄 1 paper
The longer read
The value of this cohort is that it measures what happens to pT1-T2, 1-3 node-positive women when nobody irradiates them, in a population treated with adjuvant systemic therapy almost universally. That baseline is what the absolute benefit of PMRT depends on. The randomized evidence for PMRT in this group came largely from DBCG 82b and 82c, where no-PMRT locoregional recurrence ran near 30% at 10 years. Here it is 12.7% isolated and 15.9% with simultaneous distant recurrence, closer to the BCCA randomized trial and to the systemic-therapy trial cohorts the authors cite. If the relative reduction from RT is roughly constant, as the authors assume, a lower baseline shrinks the absolute gain, and the argument for routine PMRT in every 1-3 N+ woman weakens. This paper turns that observation into a selection tool.
The tool itself deserves less confidence than the baseline does. The breakpoints were chosen by looking at which splits gave the strongest statistical separation with workable subgroup sizes, inside the same dataset, with no validation cohort. Data-driven cutpoints tend to overstate separation, and the most striking cell, 58.0% LRR±SDR in women under 45 with more than 25% of nodes positive, rests on 19 women. The more transferable result is the multivariable model: age under 45, nodal ratio above 25%, medial location and ER-negative status hold up as independent predictors on both endpoints, with hazard ratios in the 2 to 3.7 range. Even there, the nodal-ratio estimate for isolated LRR has a lower bound of 0.99.
Two selection features pull in opposite directions. Excluding the 296 women who did receive RT probably removed pts their treating physicians judged higher risk, which would push the reported baseline down and make the low-risk group look safer than an unselected population. Against that, the cohort was staged with full axillary dissection and a median of 10 nodes removed, which is more thorough than much of the trial data the authors compare against and should reduce understaging. The nodal-ratio factor depends on dissection yield, so it does not carry over to a sentinel-node-only axilla, where the denominator is small by design.
The era matters more than the paper could anticipate. Systemic therapy was AC, CMF or FAC plus tamoxifen. Better systemic control lowers locoregional recurrence on its own, so the risk-group estimates here likely overstate what a comparable pt faces now, and the model's thresholds would need recalibrating rather than applying as printed. SUPREMO was designed to answer the 1-3 node-positive PMRT question prospectively, and its result is the natural test of whether risk-adapted selection of this kind holds.
For the RT reader, the pattern-of-failure data carry practical weight: a third of regional recurrences were clavicular and very few involved the internal mammary chain, which bears on target volumes when PMRT is chosen. The paper also gives a usable framework for counselling. Below about 10% the morbidity of PMRT is hard to justify; above about 30% it is hard to withhold; the middle band is a discussion. That framing has aged better than any specific cutpoint, and it is where this study still informs a decision.