Abstract 251P
Background
This retrospective study explored a cohort of metastatic breast cancer (MBC) patients with leptomeningeal disease (LMD) who participated in a molecular screening program on tissue samples (primary tumor or metastasis).
Methods
Clinicopathological data were extracted for 22 MBC patients with LMD who underwent molecular screening (PROFILER01 (NCT01774409) or SAFIR02_Breast (NCT02299999)). Clinical outcomes were reported using the Kaplan-Meier method and compared using the log-rank test. Genomic alterations were then compared with three breast cancer databases on https://www.cbioportal.org/ (INSERM, PLoS Med 2016; METABRIC, Nature 2012 & Nat Commun 2016; MSK, Cancer Cell 2018), focusing on MBC.
Results
The median time to death from diagnosis of the first metastasis was 23.4 months (95% CI 15.5-43.8) and the median time to death from diagnosis of LMD was 1.7 months (95% CI 0.8-3.7). Molecular screening unveiled amplification of MYC (12/22; 54.5%), FGFR1 (6/22; 27.3%), and CCND1 (7/22; 31.8%). In hormone receptor-positive and HER2-negative breast cancers (13/22), FGFR1 and CCND1 were amplified in 38.5% of cases (5/13), and in triple-negative breast cancers (9/22), MYC was amplified in 77.8% of cases (7/9). BRCA1 or 2 deficiency (6/22; 27.3%) and MYC amplification were greater in LMD MBC patients than in other MBC patient databases.
Conclusions
MYC, FGFR1, CCND1 amplification, and BRCA 1/2 deficiencies are frequent genomic alterations in MBC with LMD. Targeted screening of MBC at risk of developing LMD based on these alterations could enable earlier diagnosis, before severe neurological impairment, and allow the use of more therapeutic options.
Legal entity responsible for the study
Centre Léon Bérard.
Funding
Has not received any funding.
Disclosure
L. Larrouquere: Financial Interests, Personal and Institutional, Research Grant: Seagen; Financial Interests, Personal, Other: Daiichi Sankyo, AstraZeneca, Novartis. P. Heudel: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Novartis, Seagen, Lilly, MSD, Gilead; Financial Interests, Personal, Ownership Interest: GEODAISICS. O. Tredan: Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb, MSD; Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Novartis-Sandoz, Lilly, AstraZeneca, Seagen, Daiichi Sankyo, Gilead Sciences, Eisai, Stemline, Pierre Fabre. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. All other authors have declared no conflicts of interest.