Abstract 56P
Background
HRD is correlated with increased survival of patients with advanced ovarian cancer treated with maintenance olaparib + bevacizumab. HRD is defined by pathogenic or likely pathogenic mutations of BRCA1/BRCA2 and/or a genomic instability.
Methods
Our lab is the only one performing the Myriad MyChoice test in France. The Genomic Instability Score (GIS) is calculated with the Myriad’s bioinformatics pipeline, while alterations of 11 genes are internally analyzed.
Results
From October 2022 to November 2023, we received 1009 samples from all over France. Fifty-two percent were for complete HRD testing (BRCA+GIS), whereas 48% were for GIS testing only. The mean turnaround time was 13 calendar days. The mean time between tissue sampling and receipt at our lab was 17 days for an HRD test (5.9% were over 50 days) and 35 days for a GIS testing only (20.6% were over 50 days). For a complete HRD test, only 2.3 % of samples could not be analyzed due to the lack of tumor in the sample, while for GIS more than 11% of samples did not have enough tumor material. We observed the number of GIS+ tumors decreased with the age at cancer diagnosis. More than 50% of tumors from patients younger than 50 yo were GIS+, whereas 35% of tumors were positive for patients between 50 and 75, less than 30% of tumors were positive for patients older than 75, and only 25% for patients older than 85. Of the 1009 analyses, 22.5% had inconclusive results. This was due to low/no tumor content (80.2%), low sample quality (16.3%), or consanguinity (3.5%). This thorough selection avoids false negative results. In tumors with TP53 Mutant Allele Frequency between 20-80% (good tumor content), 38% were GIS+. When TP53 MAF < 20%, meaning low tumor content, 55% were inconclusive and less than 10% were GIS+. Surprisingly, in case of high tumor ploidy (TP53 MAF > 80%), only 23% were GIS+.
Conclusions
The Myriad MyChoice test allows the analysis of BRCA variations and the GIS at the same time for a complete and faster molecular diagnosis, which is suitable for the majority of patients. Moreover, the thorough quality selection of tissue samples during the bioinformatics analysis leads to a strong reliability and a confidence in the results by dramatically reducing the rate of false negative results.
Legal entity responsible for the study
Centre Georges-François Leclerc.
Funding
Has not received any funding.
Disclosure
R. Boidot: Financial Interests, Personal, Invited Speaker: Myriad. All other authors have declared no conflicts of interest.