Abstract 2003P
Background
PARP inhibitors (PARPi) are indicated in sereval tumor types and are mostly dependent of BRCA mutation analysis that can be germline or somatic. Germline mutation analyses are performed from DNA extracted from PBMC collected from a blood sample. Somatic mutation analyses are performed from DNA extracted from tumor tissue, mostly formalin fixed parafin embedded (FFPE) samples. This different processes can lead to differences in time to results and consequently, delay before initiation of PARPi therapy with deleterious consequences for the patients.
Methods
Somatic BRCA1 and BRCA2 mutations analyses were performed using NGS, every two weeks, as 12 or 24 sample runs, using capture NGS. In all cases, prior to analysis, the specimens were macrodissected to warrant tumor cell content > 10%. Time to results were recorded from reception of the sample to sending of the report. Germline mutations NGS analysis were externalized from DNA extracted from PBMC, using the hereditary breast and ovarian cancers (HBOC) oncogenetic pathway. This study reports real life time to results delay for somatic mutation analysis.
Results
In 140 ovarian and breast cancers, median time to results for tumor analysis was 25.5 days (range 9 – 67). The maximal values were achieved in specimens with low DNA quality implying the request of a second specimen and re-analysis. The time to result for tumor molecular analysis was shorter than the median time to results achieved for germline analyses for HBOC.
Conclusions
Using frontline molecular diagnostic of BRCA somatic mutations reduces time to results as compared to germline analysis in HBOC. This could be of crucial importance for optimizing the patient care procedure and accelerating the prescription of PARPi. In BRCA mutated cases, controlling the germline origin of the identified mutations using targeted analysis from germline DNA, can lead the patients and their relatives for oncogenetic survey. This process can be upgraded to Homologous Recombinaison Deficiency (HRD) analysis and extended to all cancer types relevant of PARPi-based therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.