310P Longitudinal evaluation of circulating tumour DNA in early breast cancer using a plasma-only methylation-based assay

Plasma-only ctDNA detection is a strategy to identify molecular residual disease (MRD) in early breast cancer (EBC). MRD-positivity in the absence of clinical/radiographic disease may have prognostic implications and enable intervention prior to clinical recurrence. Plasma samples from baseline, perioperative, adjuvant and follow-up timepoints were collected in patients with estrogen receptor positive/HER2-negative (ER+) and triple-negative (TN) breast cancer treated with neoadjuvant chemotherapy (2015 onward). Samples were analyzed using the Guardant Reveal pan-tumor assay on the INFINITYTM platform. Clinical/pathologic characteristics and recurrence outcomes were collected. ctDNA/MRD-positivity was defined as a methylation score > 0. 270 timepoints (median 3 per patient, range: 1-9) were analyzed from 83 patients with ER+ (n=38) and TN (n=45) EBC; 95% (256/270) produced successful results. Baseline positivity rate was 67.5% (54/80) in all patients (66.7% in ER+, 68.2% in TN). Nine patients had a mutation called at baseline (7 PIK3CA; 1 of TP53, FGFR1, BRAF, GATA3, or NOTCH2). Larger tumor size (p=0.014) and nodal involvement (p=0.011) were associated with baseline test positivity. 17/83 (20.5%) patients have had a clinical recurrence (13 distant, 4 local). 14/17 (82.3%) patients with recurrence had a positive test at baseline (2 negative, 1 fail) and baseline methylation scores were higher in patients with recurrence (p=0.0032). Seven of 8 patients with recurrence had a positive sample collected at or prior to clinical recurrence with lead time of up to 5.1 months. Four patients with no documented recurrence had a positive test at their last follow up [range: 4.7-19.1 months from last test] with methylation scores lower than those of patients with recurrence (p=0.012). Any ctDNA positivity in follow up after surgery was strongly associated with a risk of recurrence (HR = 7.02, 95%CI: 1.82-27.2, p=0.001). This longitudinal evaluation of a plasma-only methylation based ctDNA assay demonstrates ctDNA detection and dynamic changes in a large EBC cohort. Potential prognostic and predictive applications warrant further evaluation.