Abstract 29P
Background
High TMB has been suggested as a predictive biomarker for response to immune checkpoint blockade (ICB). Several ongoing ICB trials use liquid biopsy to identify patients (pts) with hypermutated (HMT) cancer. The prevalence of HMT breast cancer (BC) defined by LB is not well described. The aim of this study was to evaluate the frequency and genomic profile of HMT BC as assessed by LB in pts with metastatic BC (mBC).
Methods
Clinical and molecular data from pts with mBC enrolled in the STING trial (NCT04932525) was analyzed. Genomic analysis was carried out by using the FoundationOne Liquid CDx assay covering analysis of 324 genes. TMB was determined by counting all synonymous and non-synonymous variants present at 5% allele frequency or greater (after filtering). Total number is reported as mutations per megabase (mut/Mb) unit. Samples were classified as HMT BC if ≥16 mutations per megabase (mut/Mb).
Results
From July 2020 to November 2022, 358 pts with mBC were included: 266 (74%) Luminal (Lum), 16(4%) HER2 positive (HER2+ve), and 76 (21%) with triple-negative (TN) mBC. The most common morphology was invasive ductal carcinoma (IDC) (n=304; 85%) followed by invasive lobular carcinoma (ILC) (n= 42; 12%). Pts had received a median of 3 lines of therapy at the time of LB. Median TMB in all cohort was 3 mut/Mb. The median TMB did not significantly vary according to the tumor subtype (Lum: 3 mut/Mb; HER2+ve:1 mut/Mb; TN: 4 mut/Mb (p=0.71)). HMT tumors were found in 16 pts (4.4% of the overall cohort). The majority of HMT tumors were Lum (75%; n=12). The remaining 25% (n=4) were TN. Additionally, 4.7% of ILC were HMT compared to 3.1% of IDC, but this difference in prevalence was not statistically significant (p=0.62). The most frequently altered genes in the HMT cohort were TP53, PIK3CA, NF1, ESR1, BRCA2. None of these pts presented microsatellite instability.
Conclusions
Hypermutated BC, measured by ctDNA, were reported in 4.4% of all pts with mBC in this cohort. These data are in agreement with the hypermutation rate described in tumor tissue in most series. Although not statistically significant, higher rate of HMT BC in metastatic ILC (4.7%) compared to metastatic IDC tumors (3.1%) was observed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.T.M.L. M Ribeiro: Financial Interests, Personal, Advisory Board: Gilead Sciences, Inc.; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: eESO. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, Msd, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Financial Interests, Institutional, Other, advisory board: Guardant Health; Financial Interests, Institutional, Other, Advisory board: MEDIMMUNE, Gilead, Relay therapeutics; Other, Founder: Pegacsy. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Invited Speaker: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. All other authors have declared no conflicts of interest.