Abstract 44P
Background
Breast cancer remains the most common cancer in India, but the genomics of advanced breast cancer (aBC) ispoorly reported. Re-biopsy at progression poses a challenge specially from bone, lungs, and brainunderscoring the opportunity for more convenient plasma genotyping.
Methods
We retrospectively analyzed results of a commercially available ctDNA NGS assay (Guardant360®) for aBCpatients in India from Nov 2018 to Apr 2024. Tests could have been ordered at different lines of treatment indifferent patients. This test evaluates single nucleotide variants (SNVs), insertions and deletions, fusions, andamplifications in 74-83 genes and, for some patients, microsatellite instability (MSI) and blood tumormutational burden (bTMB).
Results
With a ctDNA detection rate of 90.7%, 106 samples from aBC patients were included in this study, with anaverage turnaround time (TAT) of 7 days (range 3-13 days). Median age was 59 years. Most common SNVs were in PIK3CA (40%, n=42), ESR1 (25%, n=27), RB1 (9%, n=10), PTEN (6%, n=6), and AKT1 (2%, n=2). Amplifications were detected for FGFR1 (13%, n=14), EGFR (12%, n=13), MYC (11%, n=12), ERBB2 (6%, n=6), and others (Table). Fusion events in EML4-ALK, FGFR2-VCL, and RARA-CDK12 were observed in frequencies of 1% each. BRCA1/2 SNV prevalence was 22.6% (n=24; 8 BRCA1, 13 BRCA2, 3 BRCA1 & BRCA2 co-mutations), including 8 (7.5%) putative germline mutations. MSI-high status was not reported in any samples. NCCN defined clinically relevant alterations identified in 69% of samples. Notably, 18% of PIK3CA and 11% of ESR1 alterations occurred outside of loci assessed in hotspot testing. Table: 44P
Test summary
| Test summary | |
| No of Samples (n) | 106 |
| Median Age (Yrs) | 58 |
| Successful ctDNA detection rate (%) | 91 |
| TAT (days) | 7 |
| samples with clinically actionable mutations (%) | 69 |
| Common mutations in aBC | |
| PIK3CA | 40% |
| ESR1 | 25% |
| BRCA2 | 7% |
| ATM | 7% |
| BRCA1 | 7% |
| Common amplifications in aBC | |
| FGFR1 | 13% |
| EGFR | 12% |
| ERBB2 | 6% |
Conclusions
Our study reveals that the genomic landscape of aBC patients in India using ctDNA NGS is similar to tissue genotyping at a faster TAT. Uncovering uncommon PIK3CA and ESR1 alterations beyond hotspot testing. These findings emphasize the clinical utility of ctDNA based comprehensive genomic profiling for treatment guidance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Rohatgi: Financial Interests, Personal, Advisory Role: Guardant Health. R. Bharat: Financial Interests, Institutional, Full or part-time Employment: Guardant Health. S.S. Jain: Financial Interests, Personal, Stocks/Shares: Guardant Health; Financial Interests, Institutional, Full or part-time Employment: Guardant Health. N. Joshi: Financial Interests, Institutional, Full or part-time Employment: Guardant Health. A. Bahl: Financial Interests, Personal, Advisory Role: Guardant Health. All other authors have declared no conflicts of interest.