414P - The complex relationship between circulating tumor cells (CTCs) and brain metastases (BMs) in metastatic breast cancer (mBC): A retrospective pooled analysis

Background

CTCs count holds established prognostic value in mBC, with a validated cutoff of 5 CTCs/7.5 mL that allows stratification into indolent (StIV_ind; < 5) and aggressive (StIV_agg; ≥ 5) disease. BMs typically occur late in mBC, with a negative impact on survival. Our study aims to explore potential associations between CTCs and BMs in mBC patients (pts).

Methods

We conducted a retrospective pooled analysis on mBC pts from 18 cohorts, who underwent CTCs enumeration at baseline (BL), prior to initiating a new treatment line. Logistic regression tested the association between relevant prognostic factors, including CTCs count stratified according to the 5 CTCs/7.5 mL threshold, and the presence (BM_yes) or absence (BM_no) of BMs at BL. Survival was analyzed using Kaplan-Meier curves and the log-rank test.

Results

2387 pts had available BMs data and were stratified in: 1175 (49.2%) StIV_ind/BM_no, 129 (5.4%) StIV_ind/BM_yes, 981 (41.1%) StIV_agg/BM_no and 102 (4.3%) StIV_agg/BM_yes. Luminal-like (Lum), HER2-positive (HER2⁺) and triple negative (TNBC) subtypes were 60.9%, 24.0% and 15.1%, respectively; 50.2% of pts received first-line therapy. After stepwise logistic regression, no significant associations were found in the overall population (OP) and in the TNBC cohort. Instead, StIV_agg was associated with an increased risk of BMs in Lum (OR 1.88, p = 0.016) and, notably, with a decreased risk of BMs in the HER2⁺ subgroups (OR 0.44, p = 0.001). Across all subtypes, pts with StIV_agg/BM_yes disease had worse survival (PFS and OS) compared with StIV_ind/BM_no, while having either StIV_agg or BM_yes resulted only in numerical differences. Table: 414P

Conclusions

Our results suggest that CTCs count may be linked to BMs in a subtype-specific manner. Moreover, the coexistence of BMs and StIV_agg significantly worsens survival. Future studies will further elucidate these relationships and monitor their dynamics.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dr Massimo Cristofanilli.

Funding

Has not received any funding.

Disclosure

J. Pierga: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Seagen, MSD, Novartis, ExactSciences, Gilead, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Menarini, Veracyte, Pfizer, Lilly, Seagen, MSD, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Steering Committee Member: Novartis; Financial Interests, Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Funding: Servier. T.N. Fehm: Financial Interests, Other, Honoraria: Onkowissen, Medconcept, FOMF. J. Á. García Saenz: Non-Financial Interests, Advisory Role: Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Gilead, Menarini; Financial Interests, Speaker, Consultant, Advisor: Celgene, Eli Lilly, Eisai, MSD, Exact Sciences, Tecnofarma, Nolver (Adium), Asofarma, Roche; Financial Interests, Research Funding: AstraZeneca; Financial Interests, Other, Travel support: Gilead, AstraZeneca, Daiichi Sankyo. C. Caldas: Non-Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Research Funding: AstraZeneca, Genentech, Roche, Servier, Cycle Therapeutics. P. Gazzaniga: Financial Interests, Speaker, Consultant, Advisor: Merck Serono; Financial Interests, Research Funding: Amgen; Financial Interests, Other, Travel support: LeoPharma. L. De Mattos-Arruda: Financial Interests, Speaker, Consultant, Advisor: Roche; Non-Financial Interests, Funding, Research collaboration and support: NanoString Technologies; Financial Interests, Funding, Education grant: BMS, Eli Lilly; Financial Interests, Full or part-time Employment: BioNTech SE. M. Ignatiadis: Financial Interests, Personal, Invited Speaker: Novartis, Daichi, Menarini Group; Financial Interests, Personal, Other, Independent monitoring committee: Seattle Genetics; Financial Interests, Personal, Other, Grants review: Gilead Sciences; Financial Interests, Personal, Other, consultant: Rejuveron Senescence Therapeutics; Financial Interests, Institutional, Other, travel grants: AstraZeneca; Financial Interests, Institutional, Coordinating PI: Pfizer, Roche, Natera, Inivata Inc; Non-Financial Interests, Officer: EORTC. D. Generali: Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, Eli Lilly, Gilead, Menarini, Novartis, Pfizer, Roche, Seagen, Istituito Gentili, Biocartis; Financial Interests, Research Funding: Novartis, Gilead, LILT. E. Solomayer: Financial Interests, Other, Honoraria: Roche, Amgen, Celgene, Tesaro, AstraZeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson & Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre. C. Reduzzi: Financial Interests, Research Funding: Menarini Silicon Biosystems. M. Giuliano: Non-Financial Interests, Advisory Role: AstraZeneca, Daichii Sankyo, Eisai, Exact Sciences, Gilead, Eli Lilly, MSD, Novartis, Pfizer, Roche, Seagen; Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, Daichii Sankyo, Eli Lilly, MSD, Novartis, Pfizer. F. Puglisi: Financial Interests, Research Funding: AstraZeneca, Eisai, Roche; Financial Interests, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Daiichi Sankyo, Celgene, Eisai, Eli Lilly, Gilead, Exact Sciences, Ipsen, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Seagen, Takeda, Menarini, Viatris, Italfarmaco. W. Janni: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Full or part-time Employment: Universitätsklinikum Ulm; Financial Interests, Institutional, Coordinating PI: Novartis, GSK, Sanofi, Amgen, Roche, Lilly; Non-Financial Interests, Leadership Role: Chair of AGO Breast Council. L. Gerratana: Non-Financial Interests, Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, GSK, Incyte, Novartis, Pfizer, MSD, Menarini Stemline, Abbvie; Financial Interests, Research Funding: Menarini Silicon Biosystems; Financial Interests, Other, Travel expenses: Menarini Stemline. K. Pantel: Financial Interests, Personal, Advisory Board, Expert Input Forum: MSD; Financial Interests, Personal, Advisory Board, Research Presentation and Discussion: Menarini; Financial Interests, Personal, Invited Speaker, Research Presentation and Discussion: Abcam, Ipsen Pharma, Medac, Agena; Financial Interests, Personal, Advisory Board, Advisory Board: Hello Healthcare, Sanofi; Financial Interests, Institutional, Other: Angle plc; Financial Interests, Institutional, Other, UKE - European Liquid Biopsy Society (ELBS): ELBS; Financial Interests, Institutional, Other, Clinical study: Böhringer Ingelheim; Financial Interests, Institutional, Other, EFPIA Partners of EU/IMI Cancer-ID consortium: IMI JT Cancer ID. F.C. Bidard: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Novartis, AstraZeneca, GE Healthcare, SAGA Diagnostics, Daiichi Sankyo, Gilead, Inatherys; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer, Merck KGaA, Roche; Financial Interests, Institutional, Funding: Prolynx, Saga Diagnostics, Merck KGaA; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Lilly, Pfizer; Financial Interests, Personal and Institutional, Steering Committee Member: Lilly. M. Cristofanilli: Financial Interests, Speaker, Consultant, Advisor: Novartis, Genentech, Pfizer, Merck, Sanofi, Daiichi Sankyo, AstraZeneca, Eli Lilly, Gilead Sciences, Menarini, Mersana; Financial Interests, Research Funding: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, AstraZeneca, Daiichi Sankyo. All other authors have declared no conflicts of interest.