415P - Comprehensive liquid biopsy characterization of patients with metastatic inflammatory breast cancer

Background

Inflammatory breast cancer (IBC) is a rare and aggressive form of BC. Biomarkers to improve risk assessment represent an unmet need. Given the scarcity of liquid biopsy (LB) studies focusing on IBC, our aim was to provide a multi-analyte LB characterization of IBC to dissect its biology and prognosis.

Methods

This study analyzed 341 metastatic BC patients (pts) enrolled in the NU16B06 trial at Northwestern University (2016-2021). Baseline blood samples were processed with the CellSearch® system to enumerate circulating tumor cells (CTCs), HER2+ CTCs, CTCs clusters, cytokeratin+/CD45+ cells (dual-positive, DPs), and tumor-derived extracellular vesicles (tdEVs)–using the ACCEPT software. ctDNA was analyzed with the Guardant360 NGS assay. Differences in LB analytes and their association with overall survival (OS) were compared between the IBC and non-IBC subgroups.

Results

Of the 341 enrolled pts, IBC was diagnosed in 83 pts (24%). Compared to non-IBC, IBC were more frequently HER2+ or TNBC. The Table shows the differences in the distribution of circulating cellular analytes and ctDNA. CTCs, HER2+ CTCs, and tdEVs were significantly associated with OS irrespective of the IBC status. Only in IBC, DPs were significantly associated with OS (HR 2.48) and a trend for shorter OS was observed based on CTC clusters. MYC (HR 4.53) and PIK3CA (HR 3.33) gene alterations had an impact on OS for IBC, while ARID1A (HR 2.07), TP53 (HR 7.33), PIK3CA (HR 2.73), MYC (HR 3.32), CCND2 (HR 3.27) and CCND1 (HR 3.79) alterations showed an impact for non-IBC. Regarding pathways, Cell Cycle (HR 3.29) and MYC (HR 3.33) alterations showed a negative prognostic role for IBC while alterations in P53 (HR 2.08), RAS (HR 2.43), PI3K (HR 2.73), Cell Cycle (HR 2.51), and MYC (HR 3.32) pathways had an impact for non-IBC. Table: 415P

Conclusions

Although preliminary, integration of diverse circulating biomarkers showed the potential to refine prognosis, inform clinical decisions, and deepen our understanding of the biology of the IBC subtype.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

American Italian Cancer Foundation.

Disclosure

L. Gerratana: Financial Interests, Personal, Advisory Role: Lilly, Novartis, Astrazeneca,GSK, Incyte. P. D'Amico: Financial Interests, Personal, Full or part-time Employment: Merck. A.A. Davis: Financial Interests, Personal, Advisory Board: Pfizer, Biotheranostics; Financial Interests, Institutional, Research Grant: Breast Cancer Alliance; Financial Interests, Institutional, Local PI: Natera, TopAlliance Biociences, AstraZeneca, Antegene Biologics, Roche, Pfizer, Abbvie. H. Liu: Non-Financial Interests, Personal, Other: ExoMira Medicine. W.J. Gradishar: Financial Interests, Personal, Advisory Board: Astrazeneca, Roche, Novartis, Lilly; Financial Interests, Local PI: Gilead. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Editor of Chief of ESMO Open: ESMO; Non-Financial Interests, Leadership Role, Until the end of 2024: EUSOMA. M. Cristofanilli: Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Advisory Role: Lilly, Menarini, Olaris, AstraZeneca/Daiichi Sankyo, Syantra, Sermonix Pharmaceuticals, Celcuity; Financial Interests, Personal and Institutional, Funding: Lilly, Angle, Merck, AstraZeneca, Menarini Silicon Biosystems. All other authors have declared no conflicts of interest.