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
603 - Mendelian Randomization Study of Alzheimer's Disease and Lung Cancer
Presenter: Huaqiang Zhou
Session: Poster Display session 1
Resources:
Abstract
4462 - Spanish registry of thoracic tumors (TTR): Interim analyses of comorbidities, risk associations, personal and family history of cancer
Presenter: Rafael Lopez Castro
Session: Poster Display session 1
Resources:
Abstract
3957 - Pleural effusion TGF-beta is highly diagnostic and prognostic in malignant pleural mesothelioma
Presenter: Paul Stockhammer
Session: Poster Display session 1
Resources:
Abstract
3583 - Immune microenvironment modulation by p14/ARF in Malignant Pleural Mesothelioma
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4255 - Tumor Treating Fields plus chemotherapy for first-line malignant pleural mesothelioma (MPM): radiological responses in the STELLAR trial
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract
1803 - Effects of Tumor Treating Fields (TTFields; 150 kHz) and Cisplatin or Pemetrexed Combination Therapy on Mesothelioma cells In Vitro and In Vivo
Presenter: Mijal Munster
Session: Poster Display session 1
Resources:
Abstract
2660 - Real world use of systemic therapy in elderly patients with malignant pleural mesothelioma (MPM)
Presenter: Susana Cedres
Session: Poster Display session 1
Resources:
Abstract
3150 - Pemetrexed/Cisplatin versus Gemcitabine/Cisplatin as first-line treatment for Egyptian patients with malignant pleural mesothelioma
Presenter: Mohamed Alorabi
Session: Poster Display session 1
Resources:
Abstract
4319 - Accuracy of pathologic evaluation for thymic epithelial tumors in an Italian reference Centre
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
4811 - Comprehensive genomic profiling of thymic carcinoma in a sample Chinese population
Presenter: Baohui Han
Session: Poster Display session 1
Resources:
Abstract