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
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract