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Gynecol Oncol. 2019 Nov 18. pii: S0090-8258(19)31670-1. doi: 10.1016/j.ygyno.2019.11.019. [Epub ahead of print]

Clinicopathological features of women with epithelial ovarian cancer and double heterozygosity for BRCA1 and BRCA2: A systematic review and case report analysis.

Author information

1
Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada. Electronic address: cecile.le.page.chum@ssss.gouv.qc.ca.
2
Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada; Department of Pathology, Centre hospitalier de l'Université de Montreal (CHUM), Montreal, QC, Canada.
3
Institut Curie, PSL Research University, Paris, France; Department of Medical Oncology, INSERM U830 "Cancer, heterogeneity, instability and plasticity", Paris, France.
4
Gynecological Cancer Centre and Ovarian Cancer Research Group, University Hospital Basel and Department of Biomedicine, Basel, Switzerland.
5
Departments of Human Genetics, McGill University; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
6
Istituto Tumori 'Giovanni Paolo II', Bari, Italy.
7
Institut Curie, PSL Research University, Paris, France; Department of Biopathology, Paris, France.
8
Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada.
9
Institut Curie, PSL Research University, Paris, France; Department of Genetics, Paris, France.
10
Departments of Human Genetics, McGill University; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.
11
Segal Cancer Center, Lady Davis Institute of Medical research, McGill University, Montreal, QC, Canada.
12
Department of Oncology, Centre Léon Bérard, Lyon, France.
13
Department of Oncology, Hôpitaux Universitaires de Genève and Department of Medicine, Faculty of Medicine, Geneva, Switzerland.
14
Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada; Division of Gynecology-Oncology, CHUM, QC, Canada; Department of Obstetrics and Gynecology, University of Montreal, Montreal, QC, Canada.
15
Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada; Department of Medicine, University of Montreal, Montreal, QC, Canada. Electronic address: anne-marie.mes-masson@umontreal.ca.

Abstract

BACKGROUND:

Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC).

METHODS:

We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.

RESULTS:

Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).

CONCLUSIONS:

Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.

KEYWORDS:

BRCA; COEUR cohort; Heterozygosity; High-grade serous ovarian carcinoma; Hormone receptor; Survival

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