Abstract 4611
Background
Non-BRCA1/2 pathogenic variants have increasingly been associated with breast and ovarian cancer (BOC). In this study, we analyze the clinical and molecular characteristics of non-BRCA1/2 BOC identified in our program.
Methods
Index pts without BRCA1/2 pathogenic variants identified between 2004-2018, were counselled for multigene sequencing after multidisciplinary decision. Either the BRCA Hereditary Cancer MASTR Plus (Multiplicom) or the Trusight (Ilumina) were performed in the MiSeq platform (Illumina). Counselling included the possibility of opt out.
Results
From all 4277 index pts tested, 377 non-BRCA1/2 (96,3% breast and 22,6% ovarian cancer) consented on reanalysis and in 31 (8.2%) a pathogenic variant was identified. All but one (with both ATM and PALB2 mutated) pt harbored one pathogenic variant (Table). For 38 pts (10,1%) only selected genes from the panel were studied and 11 (2,9%) opted out of TP53.Table:
2009P
Gene | Pathogenic variant |
---|---|
CHECK2 | c.1100delC (1) c.319 + 2T>A (6) c.593-1G>T (1) |
PALB2 | c.1192delG (1) c.2257C>T; p.Arg753Ter (2) c.172_175delTTGT; p.Gln60ArgfsTer7 (1) c.751C>T (1)* |
RAD51C | c.404G>A; p.C135Y (2) c.709C>T;p.Arg237 (1) c.887_896del10 (1) c.8890_899delTTGTTCCTGC;p.Leu297HisfsTer2 (1) |
ATM | c.3802delG;p.Val1268Ter (1) c.8264_8268delATAAG (2)* c.8292_8293delTG; p.Ser2764ArgfsTer4 (1) |
TP53 | c.586C>T;p.Arg196Ter (1) c.725G>A (1) c.1010G>A;p.Arg337His (1) |
BLM | c.298_299delCA; p.Gln100Glufs (1) c.2206dupT; p.Tyr376LeufsTer5 (1) |
RAD50 | c.2516_2517insA;p.Asp840ArgfsTer5 (2) |
BRIP1 | c.3874 + 2T>C (1) c.484C>T; p.Arg162Ter (1) |
FAM175A | c.1106dupG;p.Ser370iLefsTer2 (1) |
Predictive factors for positive tests were a lower median age of BC diagnosis (37vs41) and a complex phenotype (9.7%vs3.8%). Neither the family male: female ratio (3,2% vs 7,2%) or prostate cancer (19.4%vs21,4%) were predictive, but other cancers were more frequent in hereditary cases (83.9%vs78,8%). All individuals were invited for prospective follow up.
Conclusions
A recurrent CHECK2 event explained 19% of all cases and opt out, as well as incomplete panels, may have underestimated the relevance of the TP53 gene. Younger age at BC diagnosis, complex phenotype and aggregation with other cancers were predictive for positive test. Additional follow up will add to the impact of non-BRCA1/2 tests in clinical practice.
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
4079 - Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy
Presenter: Gabriela Kramer-marek
Session: Poster Display session 1
Resources:
Abstract
4364 - Upregulation of sFRP3 circulating expression levels correlates survival outcomes in glioblastoma
Presenter: Gema Bruixola
Session: Poster Display session 1
Resources:
Abstract
2327 - Characterization and pre-clinical modeling of genetic aberrations in pediatric gliomas
Presenter: Itai Moshe
Session: Poster Display session 1
Resources:
Abstract
3154 - Preclinical Study of Novel Tetracyclic Small Molecule, CC12, for Brain Cancer
Presenter: Liyun Fann
Session: Poster Display session 1
Resources:
Abstract
5759 - CHLOROBRAIN phase IB trial: The addition of chloroquine, an autophagy inhibitor, to concurrent radiation and temozolomide for newly diagnosed glioblastoma
Presenter: Inge Compter
Session: Poster Display session 1
Resources:
Abstract
1382 - A Phase II Clinical Trial Evaluating the Efficacy and Safety of Apatinib Combined with dose-dense Temozolomide in Recurrent Glioblastoma
Presenter: Yong Wang
Session: Poster Display session 1
Resources:
Abstract
4407 - Phase 0 Trial of Ceritinib in Brain Metastases and Recurrent Glioblastoma
Presenter: Shwetal Mehta
Session: Poster Display session 1
Resources:
Abstract
1469 - Pembrolizumab (Pem) in recurrent high-grade glioma (HGG) patients with mismatch repair deficiency (MMRd): an observational study
Presenter: Mario Caccese
Session: Poster Display session 1
Resources:
Abstract
4217 - Outcome of high-grade gliomas (HGGs) treated into immunotherapeutic early-phase clinical trials (ieCTs): a single-center experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
5107 - Tolerability of PCV in Low Grade Glioma: a Real World Experience
Presenter: Razia Aslam
Session: Poster Display session 1
Resources:
Abstract