337P - Is presence of molecular residual disease after pathologic complete response associated with relapse in inflammatory breast cancer?

Background

Up to 30% of inflammatory breast cancer (IBC) patients develop relapse after pathologic complete response (pCR). We sought to evaluate the prognostic value of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), markers of molecular residual disease (MRD), in IBC patients with pCR after neoadjuvant chemotherapy (NAC).

Methods

Patients were enrolled in a prospective registry (2005-2022) and underwent blood draws at baseline, throughout NAC, and 6- and 12-months post-surgery. CTCs were enumerated using CellSearch^TM and ctDNA quantification was performed using Oncomine Pan-Cancer Cell-Free Assay. Patients with ≥ 1 CTC or ctDNA variant detected post-surgery were included in the positive CTC or ctDNA cohort, respectively. Wilcoxon rank-sum and Fisher’s exact tests were used to compare between groups and Kaplan-Meier method was used for survival estimates.

Results

Of the 111 patients included, median age was 50.5 years (IQR 17) and BMI was 29.3 kg/m² (11.3). Most patients were White (84, 75.7%) with stage III (93, 83.8%), node-positive (106, 95.5%), and high grade (79, 70.5%) disease. Almost all received trimodality therapy (109, 98.2%) with a pCR rate of 35.1% (39). At a median follow-up of 7.1 years (95% CI 4.7-9.4), overall survival (OS) was 72.3% and recurrence rate was 43.2%. Among the pCR cohort, post-surgery MRD rates ranged from 23.1-36%. Compared to the pCR cohort, patients without pCR had higher ctDNA positivity at 6-months post-op (50% vs. 23.1%, p = 0.08) and significantly higher CTC positivity at 12-months post-op (52.1% vs. 28.1%, p = 0.04). Presence of any CTCs after surgery led to worse OS, progression-free survival (PFS), and shorter time to recurrence (p = 0.031, 0.005, and 0.003, respectively). There were no differences in OS, PFS, and time to recurrence by ctDNA status. When CTC and ctDNA were combined, there was an overall trend of worse OS and shorter time to recurrence among patients with positive CTC/ctDNA compared to those with negative CTC/ctDNA (6-year OS: 47.1% vs. 80%, p = 0.08).

Conclusions

A high proportion of IBC patients had persistent MRD despite achieving pCR. Longitudinal assessment of the molecular landscape is necessary for optimal risk stratification in patients with IBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

NIH/NCI Cancer Center Support Grant (award number P30 CA016672), Biostatistics Resource Group.

Disclosure

All authors have declared no conflicts of interest.