83P - Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in eary high risk breast cancer: The CITUCEL trial update

Background

About 30% of women diagnosed with early-stage breast cancer (BC) will develop metastases. Circulating biomarkers are growing as potential tools to improve patient management. The CITUCEL study aims to evaluate Circulating Tumor Cells (CTCs) and Circulating Tumor DNA (ctDNA) in early high-risk BC patients treated with (neo)adjuvant chemotherapy (CT) to predict outcomes and to correlate their mutational profiles with primary tumor one.

Methods

Blood samples before and after therapy were collected. CTCs were enriched from blood and sorted using DEPArray System. CtDNA was extracted from plasma and fragmentation index was evaluated. CTCs and ctDNA mutational profiles were subsequently analyses by NGS. Primary tumor mutational status was obtained by NGS using a custom comprehensive panel. Proteomic profiling was performed by treating plasma with iST-BCT Kit and using nano-chromatography coupled with an Exactive Plus Orbitrap Q mass spectrometer.

Results

A cohort of 54 patients with invasive early BC was enrolled (32 in neoadjuvant and 22 in adjuvant CT). 43.8% of patients in the neoadjuvant setting obtained a pathological complete response (pCR). A significant correlation between a lower baseline number of total CTCs and pCR was observed (p=0.03) in the neo-adjuvant setting; this correlation was lost when considering the EpCAM-positive CTCs only (p=0.07). A positive association between pCR and higher concentrations of short fragments was also detected in this setting. Furthermore, the number of CTC showed a positive correlation with the fragmentation index (Pearson’s r = 0.58). No significant difference in CTC counts and ctDNA amount before and after treatment in the 2 cohorts, and no significant correlation with the clinico-pathological variables was observed. Proteomic profile evaluation is ongoing. Alterations, the most frequent in TP53 and PIK3CA genes, were detected in 22 patients, and approximately 40 % of those were also found in baseline ctDNA and/or CTCs.

Conclusions

Our study suggested that CTCs analysis could provide prognostic information in early BC setting and that the use of a targeted panel may be helpful to reproduce the mutational profiles of circulating molecules and primary tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Italian Health Ministry 5x1000 funding in 2016.

Disclosure

E. Blondeaux: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Research Grant, Research grant to my Institution for a research project: Gilead Science. G. Zoppoli: Financial Interests, Personal, Ownership Interest, Co-ownership: Immunomica Srl. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Writing Engagement, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Writing Engagement, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead, GSK, Eisai, Stemline Menarini; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly, Gilead; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Financial Interests, Institutional, Local PI: Gilead, Seagen; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. All other authors have declared no conflicts of interest.