SLNB vs ALND in TNBC After Neoadjuvant Chemo-Immunotherapy

Key Takeaways

• Among selected women with cN1-3, cM0 TNBC who achieved ypN0 after NAC with or without ICIs and had at least 3 examined lymph nodes, SLNB accounted for 82.5% of axillary operations.
• After NAC alone, propensity-matched 5-year overall survival was significantly lower with SLNB than with ALND.
• After NAC plus ICIs, no significant overall survival difference was detected between ALND and the NCDB-coded SLNB group, which the authors note may include some targeted axillary dissection cases without completion ALND.
• Before matching, SLNB use was higher with NAC plus ICIs than with NAC alone in cT1-2 disease and in both cN1 and cN2-3 subgroups.
• Interpretation of the chemo-immunotherapy comparison is tempered by the observational design and limited follow-up beyond 48 months.

Investigators conducted a retrospective National Cancer Database (NCDB) analysis covering 2018 through 2022 in the Li et al study of SLNB vs ALND after neoadjuvant chemo-immunotherapy in node-positive TNBC and identified women with histologically confirmed triple-negative breast cancer, cT1-4, cN1-3, cM0 disease who received neoadjuvant systemic therapy, achieved ypN0, met the study's axillary-surgery eligibility criteria including at least 3 examined lymph nodes, and underwent SLNB or ALND. The NCDB-coded SLNB group may also have included some targeted axillary dissection cases without completion ALND. The analytic cohort included 4,336 eligible patients drawn from 1,315,170 breast cancer cases in the NCDB. Neoadjuvant chemotherapy (NAC) was defined by a chemotherapy-to-surgery interval of 84 to 270 days, ALND included completion dissection after SLNB, and separate 1:1 propensity score matches were performed within the NAC-alone and NAC-plus-immune checkpoint inhibitors cohorts, yielding 449 versus 449 patients and 275 versus 275 patients, respectively. Because follow-up later diverged between treatment groups, investigators also used restricted mean survival time (RMST) at a 48-month horizon.

SLNB was the most frequently used axillary procedure overall, and before matching it was used more often with NAC plus ICIs than with NAC alone in cT1-2 disease and in both cN1 and cN2-3 subgroups. In the matched survival comparisons of SLNB and ALND in node-positive TNBC, the NAC-alone cohort had 5-year overall survival of 83% with SLNB versus 87.8% with ALND, and SLNB remained associated with worse survival after adjustment (adjusted hazard ratio 1.63; 95% CI 1.12-2.38; P=.01). In the NAC-plus-ICI cohort, 5-year overall survival was 90.1% with SLNB versus 93.6% with ALND, RMST was identical at 46.39 months over 48 months, and the adjusted hazard ratio was 1.19 (95% CI 0.54-2.61; P=.67).

Overall survival, rather than locoregional recurrence, was the available oncologic endpoint in the NCDB, so the analysis could not directly address axillary recurrence after de-escalation. The database also lacked technique details such as dual tracers, clipped-node retrieval, and a clear distinction between standard SLNB and targeted axillary dissection when no completion ALND was performed. Residual confounding may persist despite matching and multivariable adjustment, particularly in the selection of patients for ICIs or ALND. Follow-up in the chemo-immunotherapy cohort also showed substantial censoring beyond 48 months, which is why RMST at 48 months was emphasized and why later Kaplan-Meier estimates were less stable.

The authors said the survival association of axillary de-escalation appeared to differ by systemic treatment regimen, with a historical disadvantage for SLNB after NAC alone but no detected disadvantage after NAC plus ICIs. They interpreted the chemo-immunotherapy pattern as consistent with stronger systemic control potentially mitigating concern about omitting ALND and said the findings support prospective testing.

Clinician Questions

What did this NCDB analysis show about SLNB versus ALND after NAC alone in ypN0 node-positive TNBC?

In women with cN1-3, cM0 TNBC who achieved ypN0 after NAC alone, SLNB was associated with lower overall survival than ALND in the matched analysis, with 5-year OS of 83% versus 87.8% and adjusted HR 1.63 (95% CI 1.12-2.38; P=.01).

Was overall survival different between SLNB and ALND after NAC plus immune checkpoint inhibitors in ypN0 node-positive TNBC?

In selected women with cN1-3, cM0 TNBC who achieved ypN0 after NAC plus ICIs and had at least 3 examined lymph nodes, no significant overall survival difference was detected between ALND and the NCDB-coded SLNB group, which may have included some targeted axillary dissection cases without completion ALND, with 5-year OS of 90.1% versus 93.6%, identical 48-month RMST of 46.39 months, and adjusted HR 1.19 (95% CI 0.54-2.61; P=.67).

How often was SLNB used in women with ypN0 node-positive TNBC in this NCDB cohort?

In the selected NCDB cohort of women with cN1-3, cM0 TNBC who achieved ypN0 after neoadjuvant therapy and had at least 3 examined lymph nodes, SLNB was used in 3,578 of 4,336 patients, or 82.5%.

What limits interpretation of axillary de-escalation results after chemo-immunotherapy in node-positive TNBC?

Interpretation is limited because the NCDB analysis was observational, captured overall survival but not locoregional recurrence, did not record dual tracers or clipped-node retrieval, could not cleanly separate standard SLNB from targeted axillary dissection in some cases, may retain residual confounding, and had limited follow-up beyond 48 months in the chemo-immunotherapy cohort.