Abstract 431P
Background
CTCs and tdEVs predict clinical outcome in MBC pts. The detection of HER2+ CTCs has been associated with poor prognosis in HER2- MBC. In the blood of MBC pts, it is also possible to detect cytokeratin negative (CK-) CTCs. The clinical significance of HER2 expression in CK- CTCs and tdEVs is understudied.
Methods
This study retrospectively analyzed 258 pts with HER2- MBC enrolled at Northwestern University (Chicago, IL) between 2016 and 2021 (NU16B06 trial). Baseline blood samples were processed for CTCs with the CellSearch® system using an anti-HER2 antibody. CTCs were manually counted and classified according to HER2 staining intensity. The ACCEPT software was applied to evaluate HER2 status on CK- CTCs and tdEVs.
Results
122 pts (47%) had ≥ 5 CTCs/7.5 mL of blood. HER2 status of CTCs was assessed in 198 pts: 92 (47%) had ≥1 CTCs with moderate or strong staining (i.e. HER2+ CTCs). CK- HER2+ CTCs were detected in 220 pts (85%); CK+ HER2+ tdEVs were detected in 51 pts (20%). The distribution according to CTCs is shown in the table. CTCs and tdEVs were significantly associated with overall survival (OS). Overall, detection of ≥1 HER2+ CTC was associated with shorter OS (19 vs 47 months, p<0.001). In pts with ≥ 5 CTCs, HER2+ CTCs were associated with a numerical decrease in OS (25 vs 15 months; p=0.069). Pts with ≥1 CK- HER2+ CTCs had worse outcome (23 vs 33 months; p=0.029) whereas HER2+ tdEVs were not significantly associated with OS. In multivariate analysis, hormone receptor status, therapy line, CTC count, CTC-HER2 status, and tdEV count independently predicted OS. Table: 431P
CTC < 5 | CTC ≥ 5 | p value | |
CTC CK+ HER2+ | 0 [0-0] | 3 [1-9] | <0.001 |
tdEV CK+ | 4 [1-13] | 153 [51-464] | <0.001 |
CTC CK- HER2+ | 3 [1-6] | 4 [2-10] | <0.001 |
tdEV CK+ HER2+ | 0 [0-0] | 0 [0-0] | 0.461 |
tdEV CK- HER2+ | 31 [10-83] | 40 [14-98] | 0.131 |
Conclusions
HER2 expression can be detected in CTCs from HER2- MBC pts representing a prognostic factor and a possible therapeutic target. The prognostic role of CK- HER2+ CTCs suggests their tumor origin as cells with mixed epithelial-mesenchymal phenotype; additional studies on these CTCs are needed. HER2 expression on tdEVs was not associated with outcome.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Eleonora Nicolò was supported by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship.
Disclosure
P. D'Amico: Other, Personal, Full or part-time Employment: Merck & Co.. L. Gerratana: Financial Interests, Advisory Role: Lilly, Novartis, AstraZeneca, GSK, Incyte; Financial Interests, Institutional, Research Funding : AstraZeneca. A.A. Davis: Financial Interests, Advisory Role: Pfizer, BioTheranostics. H. Liu: Financial Interests, Other, Scientific co-founder: ExoMira Medicine, Inc. W.J. Gradishar: Financial Interests, Advisory Role: Genentech/Roche, AstraZeneca, Pfizer, Puma Biotechnology, Seattle Genetics, Merck, BeyondSpring Pharmaceuticals. A.N. Shah: Financial Interests, Advisory Role: AstraZeneca/MedImmune, Gilead Sciences. G. Curigliano: Financial Interests, Advisory Role: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo; Financial Interests, Other, Honoraria: Ellipses Pharma; Financial Interests, Other, fees for travel and accommodations: Roche/Genentech, Pfizer. C. Reduzzi: Financial Interests, Research Funding: Menarini Silicon Biosystems. M. Cristofanilli: Financial Interests, Other, Honoraria: Pfizer; Financial Interests, Advisory Role: Lilly, Menarini, Olaris, AstraZeneca/Daiichi Sankyo, Syantra, Sermonix, Pharmaceuticals, Celcuiy; Financial Interests, Research Funding: Lilly, Angle, Merck, AstraZeneca, Menarini Silicon Biosystems. All other authors have declared no conflicts of interest.
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