Oncologic Outcomes with De-Escalation of Axillary Surgery After Neoadjuvant Chemotherapy for Breast Cancer: Results from > 1500 Patients on the I-SPY2 Clinical Trial

Introduction: The desire to reduce patient morbidity has led to de-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) for breast cancer; however, the impact of such de-escalation on oncologic outcomes is unknown. Methods: We evaluated the relationship between axillary surgery type (sentinel lymph node [SLN] only vs. axillary lymph node dissection [ALND]) and 5-year outcomes in I-SPY2 trial patients from 2011 to 2022 who completed NAC and surgery. Rates of axillary recurrence (AxR), locoregional recurrence (LRR), distant recurrence-free survival (DRFS), and event-free survival (EFS) were compared. Results: Of 1515 patients, SLN-only was performed in 804/1014 (79.3%) ypN0 patients and 127/501 (25.3%) ypN+ patients. Median follow-up time was 3.5 years. Most patients received adjuvant radiation (73.8% of ypN0 patients and 90.8% of ypN+ patients). In ypN0 cases, there was no difference between the SLN-only and ALND groups in 5-year estimated AxR (2.0% vs. 0.8%, p = 0.57), LRR (4.6% vs. 4.4%, p = 0.72), or EFS (88.3% vs. 86.4%, p = 0.09). On multivariable analysis, SLN-only was associated with better DRFS (90.8% vs. 87.9%; hazard ratio [HR] 0.54, p = 0.04). In ypN+ cases, there was no difference between the SLN-only and ALND groups in 5-year estimated AxR (5.2% vs. 3.6%, p = 0.81), LRR (7.7% vs. 14%, p = 0.13), DRFS (70.0% vs. 66.7%, p = 0.09), or EFS (70.4% vs. 63.2%, p = 0.07). Conclusions: With short-term follow-up, omission of ALND in selected patients was not associated with worse AxR, LRR, DRFS, or EFS in patients with ypN0 or ypN+ disease. While prospective trial results are awaited, these data suggest that ALND may not be necessary for all patients with residual nodal disease after NAC.