Abstract 3212
Background
The application of the Next Generation Sequencing (NGS) technology has facilitated multigene panel testing for hereditary breast cancer (BC) in clinical practice. We performed a retrospective analysis of individuals referred for testing in our lab aiming to investigate the contribution of included genes and evaluate current genetic testing guidelines in BC.
Methods
In total, 1141 BC patients and 184 unaffected individuals with family history (FH) of BC were referred from physicians for testing using a multigene panel. Genomic DNA was enriched for targeted regions of 33 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated computationally and by Multiplex Ligation-dependent Probe Amplification (MLPA).
Results
A pathogenic variant (PV) was identified in 22% (291/1325) of analyzed individuals and in specific in 23.2% of BC patients and 14.1% of unaffected individuals (P = 0.006). Among individuals with PVs, 49.1% were located in the BRCA1/2 genes whereas 8.6%, 22.7% and 19.6% occurred in other high, moderate and low-risk genes respectively. Notably, 21 of the 291 positive individuals (7.2%) carried clinically significant variants in two different genes and 6.5% had a LGR. A retrospective analysis of positive individuals showed that 88.3% of BC patients met the NCCN criteria for further genetic risk evaluation compared to 80.8% of unaffected individuals with FH of BC (P = 0.269). In BRCA-positive cases, NCCN criteria were met in 92.3% of the referrals compared to 81.8% in individuals positive for other genes (P = 0.008).
Conclusions
Extended multigene panel testing in hereditary BC facilitates the detection of nearly twice as many individuals that could benefit from personalized management. In our cohort, the currently used selection criteria for HBOC failed to identify only 12.7% of individuals positive for pathogenic variants, suggesting strong selection strategies from physicians. However, our results indicate that selection criteria perform better for the identification of BRCA-positive BC patients and should be revised to facilitate towards the inclusion of BC patients with PVs in other genes.
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.
Resources from the same session
3611 - Phase II trial of SM 88 in Non-Metastatic Biochemical Recurrent Prostate Cancer.
Presenter: Benjamin Gartrell
Session: Poster Display session 3
Resources:
Abstract
2492 - A phase 1 study of Ad5 PSA/MUC-1/Brachyury Vaccine in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)
Presenter: Marijo Bilusic
Session: Poster Display session 3
Resources:
Abstract
3142 - Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer
Presenter: Douglas McNeel
Session: Poster Display session 3
Resources:
Abstract
4327 - Impact of germline mutations in Homologous Recombination (HR) genes on the response to Radium-223 for metastatic castration resistant prostate cancer (mCRPC)
Presenter: Elena Castro
Session: Poster Display session 3
Resources:
Abstract
3600 - Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with Radium-223 (Ra223): Results from a prospective multicentre study
Presenter: Nuria Romero Laorden
Session: Poster Display session 3
Resources:
Abstract
3742 - Prognostic value of tumor suppression genes (TP53, PTEN, Rb) in metastatic hormone sensitive prostate cancer
Presenter: Miguel Gonzalez Velez
Session: Poster Display session 3
Resources:
Abstract
2643 - Germline sequencing of advanced prostate cancer patients in the BARCODE2 trial
Presenter: Sarah Benafif
Session: Poster Display session 3
Resources:
Abstract
4349 - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): data from the prospective PROREPAIR-B study.
Presenter: Carlo Cattrini
Session: Poster Display session 3
Resources:
Abstract
3301 - Implications of Single Nucleotide Polymorphisms (SNPs) in Androgen Related-Genes in Outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (Abi) and Enzalutamide (Enza)
Presenter: Isabel Aragon
Session: Poster Display session 3
Resources:
Abstract
2275 - Activating mutations in AKT1/PIK3CA are associated with poor clinical outcomes in metastatic prostate cancer (mPC)
Presenter: Simon Fu
Session: Poster Display session 3
Resources:
Abstract