Abstract 54P
Background
As the most common special subtype of breast cancer (BC), invasive lobular carcinoma (ILC) displays different clinical and histological features, especially in the metastatic setting. As ILC is frequently hormone receptor-positive (HR+), HER2 negative (HER2-), we compared ctDNA in patients with stage IV ILC to patients with stage IV HR+, HER2- BC with non-special type (NST).
Methods
From an initial cohort of 84 HR+/HER2- patients with metastatic breast cancer we selected 77 patients diagnosed with NST, N=61, or ILC, N=16. We analyzed circulating tumor DNA (ctDNA) from plasma samples before initiating first or second-line endocrine-based therapy. Tumor fractions were estimated using mFAST-SeqS, an untargeted aneuploidy detection method, and presented as z-scores. Additionally, the AVENIO ctDNA Expanded 77-gene panel was used to characterize the mutational landscape of ctDNA across histologies. For this analysis, we included single nucleotide variants (SNVs) classified as pathogenic, likely pathogenic, or of unknown significance.
Results
Analysis revealed that84% (65/77) of patients had detectable ctDNA alterations. The percentage did not significantly differ between patients with NST vs ILC (94% for ILC and 82% for NST, p=0.441). Although ctDNA from patients with ILC demonstrated a higher median z-score than that from patients with NST, the difference did not reach statistical significance (median 3.32 vs. 1.85, p=0.112). Patients with ILC had a significantly higher number of SNVs than those with NST (median 4.0 vs. 2.5; p=0.042). No differences in mutant allele frequency were noted. Among metastatic NST cases, the most prevalent alterations were in PIK3CA (38%), TP53 (26%), ESR1 (20%), PTEN (11%), and BRCA1 (10%). For ILC, the predominant alterations were in PIK3CA (56%), AR (19%), EGFR (19%), ESR1 (19%), and KDR (19%). Although PIK3CA, AR, and EGFR alterations were more common in ILC than in NST, these differences were not statistically significant (all p>0.05).
Conclusions
In ILC, PIK3CA, AR, and EGFR alterations and higher z-scores were more common but did not reach statistical significance. The numbers of SNV were significantly higher in patients with ILC.
Legal entity responsible for the study
Medical University of Graz, Division of Oncology.
Funding
Novartis, AstraZeneca and Pfizer (clinical documentation).
Disclosure
E.V.V. Klocker: Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Novartis; Financial Interests, Personal, Other, Travel fees: Gilead, Daiichi Sanyo, AstraZeneca, Pierre Fabre. C. Suppan: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Pfizer, Eli Lilly, Pierre Fabre, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Eli Lilly, Pierre Fabre, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Sponsor/Funding: Roche, Novartis, Astellas, AstraZeneca, Daiichi Sankyo, Pierre Fabre. S. Hasenleithner: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca; Other, Personal, Advisory Board: CureMatch ; Financial Interests, Personal, Other, Educational grant in non related agreement: Roche. A. Lee: Financial Interests, Personal, Stocks/Shares: Ocean Genomics, Almaden Genomics; Financial Interests, Personal, Other, Honoraria: Ocean Genomics, Almaden Genomics. M. Balic: Financial Interests, Personal and Institutional, Funding: Amgen, AstraZeneca, Daiichi Sanyo, Eli Lilly, Gilead, MSD, Novartis, Pierre Fabre, Pfizer, Seagen, Stemline; Financial Interests, Personal, Other, Consulting fees and lectures: Amgen, AstraZeneca, Celgene, Daiichi Sanyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Samsung, Gilead, Seagen, Stemline; Financial Interests, Personal, Other, Travel fees: AstraZeneca, Daiichi Sanyo, MSD, Roche. All other authors have declared no conflicts of interest.