Abstract 26P
Background
Circulating tumor DNA (ctDNA) assessment in blood is being studied as a biomarker in breast cancer. We aimed to assess the clinical value of ctDNA in patients with early breast cancer.
Methods
Systematic search of databases (PubMed, Embase, CENTRAL) up to 23/Nov/22 and conferences proceedings (ASCO, ESMO, AACR, SABCS, ESMO Breast) 2020-2022 was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS), and overall survival (OS) in patients with stage I-III breast cancer (PROSPERO ID: CRD42021286591). ctDNA assays were classified as tumor-informed and non-tumor informed. Timepoints of ctDNA collection were grouped as baseline (BL), after neoadjuvant therapy (End-of-NAT), and during follow-up period (FUP). Univariable (Uv) and multivariable (Mv) hazard ratios (HR) were pooled using random-effects models and reported with their 95% confidence intervals (CI).
Results
Of 3,174 identified records, 57 studies were included in this analysis reporting data from 5,729 patients with early breast cancer. 44.5% had breast cancer stage reported (18.3%, 60.0%, and 21.5% had stages I, II, and III, respectively). We found a statistically significant association of ctDNA detection at any timepoint with worse DFS and OS (Table). Pooled HRs were numerically higher when ctDNA was detected at end-of-NAT or FUP than at BL, and for tumor-informed compared to non tumor-informed assays. ctDNA detection sensitivity and specificity for breast cancer relapse ranged from 0.31-1.0 and 0.7-1.0, respectively. The mean lead time to radiological recurrence was 10.81 months (0-58.9). Table: 26P
| Timepoint | HR (95%CI) | Tumor-informed | Non tumor-informed | Overall | |
| DFS | BL | Uv | 4.2 (1.8-9.8) | 2.8 (1.7-4.6) | 3.0 (1.9-4.6) |
| Mv | 1.9 (1.1-3.2) | 2.7 (2.0-3.8) | 2.5 (1.9-3.3) | ||
| End-of-NAT | Uv | 8.9 (5.1-15.4) | 4.4 (2.6-7.2) | 7.7 (4.8-12.2) | |
| Mv | 9.9 (2.7-35.5) | 2.7 (1.3-5.8) | 5.5 (2.4-12.8) | ||
| FUP | Uv | 16.0 (8.4-30.6) | 14.0 (7.5-26.1) | ||
| Mv | 12.2 (2.8-53.3) | 2.6 (1.1-6.3) | 7.2 (2.8-6.3) | ||
| OS | BL | Uv | 2.6 (1.5-4.7) | 2.8 (1.6-4.8) | |
| Mv | 3.0 (1.4-6.4) | ||||
| End-of-NAT | Uv | 2.6 (1.0-6.4) | 2.7 (1.4-5.1) | ||
| Mv | 12.9 (0.4-380.2) | ||||
| FUP | Uv | 22.7 (9.3-55.7) | 4.0 (2.3-7.0) | 9.2 (3.3-25.9) | |
| Mv | 6.7 (0.2-224.4) | 6.2 (3.1-12.4) | 5.6 (1.5-21.8) |
Conclusions
ctDNA detection is associated with worse DFS and OS in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays. ctDNA detection has a high specificity for the diagnosis of breast cancer relapse.
Legal entity responsible for the study
Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Academic Trials Promoting Team (ATPT), Brussels, Belgium.
Funding
Has not received any funding.
Disclosure
G. Nader Marta: Financial Interests, Other, Travel grants to attend meetings: Roche, Bayer. E. Agostinetto: Financial Interests, Personal, Advisory Board: Eli Lilly, Sandoz, AstraZeneca; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Personal, Other, Support for attending medical conferences: Novartis, Roche, Eli Lilly, Genetic, Instituto Gentili, Daiichi Sankyo. D. Martins Branco: Financial Interests, Personal, Advisory Board: Angelini, AstraZeneca, Janssen, Merck Sharp & Dohme, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Merck Sharp & Dohme, Novartis; Financial Interests, Personal, Other, meeting/travel grant: Gilead Sciences, Ipsen, Janssen, LEO Farmacêuticos, Laboratórios Vitória, Pfizer, Roche; Financial Interests, Personal, Other, Meeting/travel grant.: Merck Sharp & Dohme, Novartis; Financial Interests, Institutional, Research Grant, Institutional funding for an observational research project.: Novartis; Financial Interests, Institutional, Research Grant, Institutional funding for an investigator-initiated clinical trial.: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Invited Speaker: Associação de Investigação e Cuidados de Suporte em Oncologia - Portuguese MASCC affiliate; Non-Financial Interests, Leadership Role, Portuguese Young Oncologists Committee Chair: November 2020 - May 2022: Sociedade Portuguesa de Oncologia; Non-Financial Interests, Leadership Role, Oncology Committee Chair: January 2020 - January 2021: Health Parliament Portugal. M. Ignatiadis: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Independent monitoring committee: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Natera, Inivata Inc; Non-Financial Interests, Officer: EORTC. G. Pruneri: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Exact Sciences, Novartis; Financial Interests, Personal, Advisory Board: Exact Sciences, ADS Biotec; Financial Interests, Institutional, Research Grant: Roche. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Invited Speaker: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Invited Speaker, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead; Financial Interests, Invited Speaker, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Invited Speaker, AURORA: Breast International Group; Financial Interests, Invited Speaker, Olympia: Astra-Zeneca; Financial Interests, Personal, Other, Travel grant: Astra-Zeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society for Cardiology (ESC); Non-Financial Interests, Advisory Role, Belgium governmental institution for cancer: KCE; Non-Financial Interests, Other, Editorial board member: ESMO Open; Non-Financial Interests, Advisory Role: Anticancer Fund. S. Di Cosimo: Financial Interests, Personal, Other, Ad hoc project/protocol reviewer: MEDSIR; Financial Interests, Personal, Advisory Board, Treatment of HER2-positive breast cancer: Pier Fabre; Financial Interests, Personal, Other, Medical meeting material setup and distribution; speaker bureau.: IQVIA. All other authors have declared no conflicts of interest.