Outcomes in Exceptionally Poor-Responders to Neoadjuvant Chemotherapy.

PURPOSE/OBJECTIVE(S) The use of neoadjuvant chemotherapy (NAC) in patients with operable breast cancer allows for assessment of treatment response, and subsequent tailoring of adjuvant therapy. While there is robust evidence demonstrating worse prognosis with residual disease versus path CR after NAC, there is little data regarding outcomes among patients with a heavy residual tumor burden after NAC. We report outcomes in patients who have exceptionally poor responses to NAC-those with > 9 nodes after NAC or with 5 cm or more of residual disease in the breast. MATERIALS/METHODS Between 06/2014 and 04/2020, 1511 patients received NAC followed by surgery at our institution. Poor responders, defined as those with positive nodes or residual tumor in the breast, were identified for analysis. Those with 1-3 positive nodes after NAC were used as a comparison cohort. Recurrence and survival outcomes were compared based on residual disease burden after NAC. Clinicopathologic parameters were summarized with descriptive statistics. Overall survival and recurrence-free survival estimates were calculated using Kaplan Meier methodology. RESULTS Among 517 poor-responders, 315 patients had 1-3 positive nodes (N1a), 108 had 4-9 positive nodes (N2a), and 62 had > 9 positive nodes (high-volume residual, HVR); 32 patients with > 5cm of residual tumor in the breast were categorized as HVR. With a median follow-up of 39 months (IQR 27-50), the 5-year overall survival rate was 90% among N1a, 72% among N2a, and 78% among HVR patients (P = 0.003). The 5-year distant recurrence-free survival and local recurrence-free survival rates were 87%/87% among N1a vs. 59%/71% among N2a vs. 68%/75% among HVR (P < 0.001 and P = 0.009), respectively. 5-year local-regional and distant recurrence cumulative incidence rates, stratified by residual disease burden and by breast cancer subtype, are shown in Table 1. CONCLUSION Our work confirms that patients with high-volume residual are at high risk for LR and distant recurrence as well as death, despite best available standard-of-care treatment. ypN2a patients appear to perform as bad as HVR patients in terms of DM and death, but better in terms of local-regional recurrence. Triple-negative patients with residual disease had high rates of recurrence and death compared to other subtypes. Treatment intensification efforts are urgently needed.