P5: In-Breast Tumor Progression During Neoadjuvant Chemotherapy- Impact on and Factors Influencing Distant Recurrence-Free Survival

Introduction: INTRODUCTION: Neoadjuvant chemotherapy (NAC) is commonly used in breast cancer. While most patients exhibit stable, partial or complete response to NAC, a small proportion progress. We aimed to characterize factors predicting in-breast tumor progression and the impact of progressive disease (PD) on distant recurrence. 

Methods: METHODS: We reviewed clinical and pathologic data from patients with stage I-III breast cancer treated with NAC 2006-2021. We compared outcomes of patients with in-breast PD, defined as ≥ 20% increase in tumor size per RECIST to those with stable disease (SD) or response. Distant recurrence-free survival (DRFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. 

Results:

Results: 1500 patients underwent NAC of which 73 (5%) experienced in-breast PD, 560 (37%) had breast pathologic complete response (pCR, ypT0/Tis), 597 (40%) had partial response (PR), and 270 (18%) had SD. Of those with PD, more patients had HR+/HER2- tumors (64% HR+/HER2-, 23% TNBC, 12% HER2+) than those without PD (39% HR+/HER2-, 26% TNBC, 35% HER2+), p< 0.001.  Patients with PD less frequently had IDC histology (58% vs 71%) and more frequently ILC (8% vs 3%) and inflammatory BC (8% vs 2%) (p< 0.001). Among patients with PD, 57/73 (78%) were ypN+. Post-NAC grade distribution was 14% [10/73] grade 1, 44% [32/73] grade 2, and 42% [31/73] grade 3 with 58 (79%) grade unchanged pre- and post-NAC.   

With median 50 months follow-up, 31/73 patients with PD developed distant recurrence. DRFS in patients with PD was 56% at 5 years, which was significantly worse than patients with SD (68%), PR (80%), or breast pCR (92%), p< 0.001. DRFS in patients with PD did not differ by ypN status but did differ by ypT category (p=0.004), post-NAC tumor grade (p=0.02) and receptor status (p=0.02 with HR+/HER2- having better outcome). On multivariable analysis, post-NAC grade (adjusted HR 3.1, p=0.004 for 3 vs 1-2) and ypT category (adjusted HR 3.5, p=0.01 for ypT3-4 vs ypT1-2) were the strongest predictors of DRFS in patients with PD. Combining these two factors, 25% had neither, 44% had one, and 32% had both factors, which stratified outcome in the setting of PD with 3-year DRFS of 100%, 74%, and 30%, respectively (p< 0.001, see Figure). 

Conclusions: CONCLUSIONS: While in-breast disease progression during NAC remains rare, comprising only 5%, it predicts a poor overall survival outcome. Among patients with in-breast disease progression p</span>ost-NAC tumor grade and T category are predictors of outcome and may be useful to guide escalation of adjuvant treatment recommendations.  

Learning Objectives:

• Define factors predicting in-breast tumor progression in patients with breast cancer undergoing neoadjuvant chemotherapy.
• Describe the impact of tumor characteristics on distant recurrence-free survival in patients with disease progression who have undergone neoadjuvant chemotherapy.
• Characterize the impact of progressive disease on distant recurrence-free survival in patients with breast cancer undergoing neoadjuvant chemotherapy.