Abstract 293P
Background
Liquid biopsy, including circulating tumor DNA (ctDNA), is gaining momentum in MBC characterization and monitoring. The aim of this study was to explore the interplay between ctDNA and serum biomarkers with respect to metastatic spread and tumor burden.
Methods
A total of 83 patients (pts) with luminal-like MBC enrolled in the CRO-2018-56 prospective study was treated with first line endocrine therapy and CDK4/6 inhibitors and characterized for ctDNA through droplet digital PCR at baseline (BL) and after three months, at the first radiological evaluation (E1). Associations between clinicopathological characteristics, ctDNA and serum biomarkers were tested through Kruskal-Wallis test. Variations between BL and E1 were tested through Wilcoxon sign-rank test.
Results
At BL, 31% pts had ≥ 3 metastatic sites (vs 25% at E1). Bone was involved in 72% (vs 68% at E1) of pts, liver mts in 29% of pts (vs 28% at E1), lung mts in 22% of pts (vs 22% at E1), node mts in 54% of pts (vs 43% at E1). ctDNA-detected ESR1 mutations (muts) and PIK3CA muts were found in 11% and in 28% of pts, respectively. ESR1 muts were associated with liver metastases (mts) (P < 0.0001) and a higher number of metastatic sites (met_sites) (P = 0.0304). ACTB short fragments (ACTB_s) were significantly higher in pts with node mts (P = 0.0428). Liver mts, serosal mts and higher met_sites were associated with ESR1 muts (respectively, P < 0.0001, P = 0.038 and P = 0.0135). Liver mts were also associated with higher methylation of ESR1 promoter B (promB) (P = 0.046). In pts that did not progress at E1, met_sites and ACTB_s significantly decreased at E1 vs BL (respectively, P = 0.0005 and P < 0.0001). A significant increase was observed for promA and B (respectively, P = 0.00139 and P = 0.0084), while no significant changes were observed for CEA, CA15.3 and total ctDNA yield.
Conclusions
The present study showed a strict association between ctDNA, tumor burden and metastatic pattern in luminal-like MBC. Changes in biomarkers were consistently observed at the different timepoints, further supporting ctDNA as a key tool for disease monitoring.
Clinical trial identification
CRO-2018-56.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ricerca Finalizzata Italian Ministry of Health.
Disclosure
S. Spazzapan: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Gentili; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Tesaro; Financial Interests, Personal, Invited Speaker: Pfizer. L. Gerratana: Non-Financial Interests, Personal, Other: Menarini Silicon Biosystems; Financial Interests, Personal, Other, fee: Lilly. F. Puglisi: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant, and fee: Roche; Financial Interests, Personal and Institutional, Other: Eli Lilly; Financial Interests, Personal, Other, fee: Amgen; Financial Interests, Personal, Other, fee: Ipsen; Financial Interests, Personal, Other, fee: Merck Sharp & Dohme (MSD); Financial Interests, Personal, Other, fee: Takeda; Financial Interests, Personal, Other, fee: Eisai; Financial Interests, Personal, Other, fee: Novartis; Financial Interests, Personal, Other, fee: Pfizer. All other authors have declared no conflicts of interest.