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Poster Display session 1

4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program


28 Sep 2019


Poster Display session 1


Pathology/Molecular Biology

Tumour Site

Ovarian Cancer;  Breast Cancer


Ana Monteiro


Annals of Oncology (2019) 30 (suppl_5): v797-v815. 10.1093/annonc/mdz269


A. Monteiro1, P. Machado2, A.I. Clara3, A. Opinião3, A. Luis3, I. Miguel3, P. Louro4, S. Santos2, S. Fragoso2, P. Rodrigues4, F. Rodrigues4, I. Coelho4, J. Parreira4, F. Vaz3

Author affiliations

  • 1 Medical Oncology, Instituto Portuguès de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPOLFG EPE), 1099-023 - Lisbon/PT
  • 2 Clínica De Risco Familiar; Unidade De Investigação Em Patobiologia Molecular;, Instituto Portuguès de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPOLFG EPE), 1099-023 - Lisbon/PT
  • 3 Medical Oncology; Clínica De Risco Familiar, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., 1099-023 - Lisboa/PT
  • 4 Clínica De Risco Familiar, Instituto Portuguès de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPOLFG EPE), 1099-023 - Lisbon/PT


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Abstract 4611


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.


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.


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:


GenePathogenic variant
CHECK2c.1100delC (1) c.319 + 2T>A (6) c.593-1G>T (1)
PALB2c.1192delG (1) c.2257C>T; p.Arg753Ter (2) c.172_175delTTGT; p.Gln60ArgfsTer7 (1) c.751C>T (1)*
RAD51Cc.404G>A; p.C135Y (2) c.709C>T;p.Arg237 (1) c.887_896del10 (1) c.8890_899delTTGTTCCTGC;p.Leu297HisfsTer2 (1)
ATMc.3802delG;p.Val1268Ter (1) c.8264_8268delATAAG (2)* c.8292_8293delTG; p.Ser2764ArgfsTer4 (1)
TP53c.586C>T;p.Arg196Ter (1) c.725G>A (1) c.1010G>A;p.Arg337His (1)
BLMc.298_299delCA; p.Gln100Glufs (1) c.2206dupT; p.Tyr376LeufsTer5 (1)
RAD50c.2516_2517insA;p.Asp840ArgfsTer5 (2)
BRIP1c.3874 + 2T>C (1) c.484C>T; p.Arg162Ter (1)
FAM175Ac.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.


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.


Has not received any funding.


All authors have declared no conflicts of interest.

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