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
5995 - Invasive fungal diseases caused by rare pathogens in patients after hematopoietic stem cell transplantation (HSCT) & chemotherapy
Presenter: Yuliya Rogacheva
Session: Poster Display session 1
Resources:
Abstract
2961 - Safety and pharmacokinetics of novel CXCR4 antagonist YF-H-2015005 in the mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma
Presenter: Weiping Liu
Session: Poster Display session 1
Resources:
Abstract
5771 - Chemotherapy associated Hyponatremia in Hematological Malignancies: A retrospective study of 189 patients treated in a single medical center
Presenter: Vadim Lesan
Session: Poster Display session 1
Resources:
Abstract
1165 - Risk factors for Bacteremia-Associated Mortality of Aeromona sobria in Hematologic Malignancies
Presenter: Gabriel De la Cruz-Kú
Session: Poster Display session 1
Resources:
Abstract
5287 - Use of droplet digital polymerase chain reaction for detecting minimal residual disease: a prospective, multi-institutional study
Presenter: Hyunkyung Park
Session: Poster Display session 1
Resources:
Abstract
1886 - RUBIH2 — Use of NGS in haematological malignancies: from real world data to national recommendations, an innovative program to evaluate the impact of healthcare technology on patient care
Presenter: Severine Coquerelle
Session: Poster Display session 1
Resources:
Abstract
1940 - Outcomes of chronic myeloid leukemia with T315I mutation in the absence of targeted therapy or hematopoietic stem cell transplantation
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1946 - Is bone marrow examination indispensible in chronic myeloid Leukemia at diagnosis ?
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1904 - Incidence of Imatinib Resistance in Chronic Myeloid Leukemia (CML) Patients: Experience from Resource Poor Centre of Eastern India
Presenter: Debmalya Bhattacharyya
Session: Poster Display session 1
Resources:
Abstract
3245 - BCR-ABL transcript variant’s significance in chronic myeloid leukemia in chronic phase: Institutional experience from a developing country
Presenter: Siva Prasad
Session: Poster Display session 1
Resources:
Abstract