BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management

Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.

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Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations

Cancers ◽

10.3390/cancers11030416 ◽

2019 ◽

Vol 11 (3) ◽

pp. 416 ◽

Cited By ~ 14

Author(s):

Ainhoa Madariaga ◽

Stephanie Lheureux ◽

Amit Oza

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Repair Process ◽

Resistance Mechanisms ◽

Tumour Suppressor Genes ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Damage Repair ◽

Brca Mutation Carriers ◽

Drug Efflux Pumps

High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.

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Decision aids for female BRCA mutation carriers: a scoping review protocol

BMJ Open ◽

10.1136/bmjopen-2020-045075 ◽

2021 ◽

Vol 11 (7) ◽

pp. e045075

Author(s):

Sarah A McGarrigle ◽

Geraldine Prizeman ◽

Carol Spillane ◽

Niamh Byrne ◽

Amanda Drury ◽

...

Keyword(s):

Ovarian Cancer ◽

Risk Management ◽

Scoping Review ◽

Brca Mutation ◽

Decision Aids ◽

Management Strategies ◽

Mutation Carriers ◽

Risk Management Strategies ◽

Brca Mutation Carriers ◽

Cancer Risk Management

IntroductionWomen who inherit a pathogenic mutation in Breast Cancer Susceptibility Genes 1 or 2 (BRCA1 or BRCA2) are at substantially higher risk of developing breast and ovarian cancer than the average woman. Several cancer risk management strategies exist to address this increased risk. Decisions about which risk management strategies to choose are complex, personal and multifactorial for these women. This scoping review will map evidence relevant to cancer risk management decision making in BRCA mutation carriers without a personal history of cancer. The objective is to identify and describe the features of patient decision aids that have been developed for BRCA mutation carriers. This information may be beneficial for designing new decision aids or adapting existing decision aids to support decision making in this population.Methods and analysisThis scoping review will be conducted according to the Joanna Briggs Institute’s scoping review methodological framework. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist will be used for guidance. Studies on decision aids for women with a BRCA mutation who are unaffected by breast or ovarian cancer will be considered for inclusion. Five electronic databases will be searched (MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science) with no restrictions applied for language or publication date. Studies for inclusion will be selected independently by two review authors. Data will be extracted using a predefined data extraction form. Findings will be presented in tabular form. A narrative description of the evidence will complement the tabulated results.Ethics and disseminationEthical approval for conducting this scoping review is not required as this study will involve secondary analysis of existing literature. Findings will be published in a peer-reviewed journal and presented at relevant conferences.

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Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

Cancer Control ◽

10.1177/107327480701400403 ◽

2007 ◽

Vol 14 (4) ◽

pp. 330-337 ◽

Cited By ~ 4

Author(s):

Dawn C. Allain ◽

Kevin Sweet ◽

Doreen M. Agnese

Keyword(s):

Medical Management ◽

Cancer Susceptibility ◽

Brca Mutation ◽

Brca2 Gene ◽

Brca1 And Brca2 ◽

Management Options ◽

Cancer Susceptibility Genes ◽

Mutation Carriers ◽

Increased Risk ◽

Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

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Recommendations and Choices for BRCA Mutation Carriers at Risk for Ovarian Cancer: A Complicated Decision

Cancers ◽

10.3390/cancers10020057 ◽

2018 ◽

Vol 10 (2) ◽

pp. 57 ◽

Cited By ~ 13

Author(s):

Kelsey Lewis ◽

Karen Lu ◽

Amber Klimczak ◽

Samuel Mok

Keyword(s):

Ovarian Cancer ◽

At Risk ◽

Brca Mutation ◽

Mutation Carriers ◽

Brca Mutation Carriers

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Factors influencing women’s decisions to getting tested for BRCA mutation

Journal of Nursing Education and Practice ◽

10.5430/jnep.v9n3p33 ◽

2018 ◽

Vol 9 (3) ◽

pp. 33 ◽

Cited By ~ 1

Author(s):

Suha Al-Oballi Kridli ◽

Holly Austin

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Genetic Mutations ◽

Inclusion Criteria ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Factors Influencing ◽

Brca1 And Brca2 Mutations ◽

Internal And External Factors

Ovarian cancer is the leading cause of death among gynecological cancers. There are many risk factors that can increase a woman’s susceptibility to breast and ovarian cancers, some of which are modifiable. However, non-modifiable risks for breast and ovarian cancer include the presence of genetic mutations (BRCA) increase the risk of these diseases. The purpose of this review was to identify factors, reported in the literature, known to affect women’s decision to get genetic testing for BRCA1 and BRCA2 mutations for hereditary breast and ovarian cancer. A total of 31 studies that met the inclusion criteria were included in this review. Several internal and external factors, influencing women’s decision to getting tested for BRCA mutations, were identified and explained. Implications for clinical practice were provided.

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Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-017-5995-z ◽

2017 ◽

Vol 24 (11) ◽

pp. 3116-3123 ◽

Cited By ~ 5

Author(s):

Charlotte Gamble ◽

Laura J. Havrilesky ◽

Evan R. Myers ◽

Junzo P. Chino ◽

Scott Hollenbeck ◽

...

Keyword(s):

Ovarian Cancer ◽

Cost Effectiveness ◽

Brca Mutation ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

History Of ◽

Risk Reducing

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Prevalence of BRCA1 and BRCA2 genes mutations in a sample of families with high risk of breast and ovarian cancer in Brazil.

10.1158/0008-5472.sabcs-6020 ◽

2009 ◽

Author(s):

VF Esteves ◽

LS Thuler ◽

L Amendola ◽

PP Frankel ◽

RJ Vieira ◽

...

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Brca1 And Brca2 Genes

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Abstract LB-255: Exome mutation burden predicts clinical outcome in ovarian cancer carrying mutated BRCA1 and BRCA2 genes.

10.1158/1538-7445.am2013-lb-255 ◽

2013 ◽

Author(s):

Nicolai Juul Birkbak ◽

Bose Kochupurakkal ◽

Jose MG Izarzugaza ◽

Yang Li ◽

Joyce Liu ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Outcome ◽

Brca1 And Brca2 ◽

Mutation Burden ◽

Brca1 And Brca2 Genes

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Factors Impacting on Decision-Making towards Prophylactic Surgeries in BRCA Mutation Carriers and Women with Familial Predisposition

Breast Care ◽

10.1159/000503370 ◽

2019 ◽

Vol 15 (3) ◽

pp. 253-259

Author(s):

Robin Segerer ◽

Clara Peschel ◽

Ulrike Kämmerer ◽

Sebastian Häussler ◽

Achim Wöckel ◽

...

Keyword(s):

Ovarian Cancer ◽

Decision Making ◽

Brca Mutation ◽

Prophylactic Surgery ◽

Sexual Life ◽

Familial Predisposition ◽

Emotional Factors ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Psychological Predictor

Background/Objectives: BRCA mutation carriers and women at high risk of breast/ovarian cancer are faced with the intricate question to opt for prophylactic surgeries and/or a periodic screening. The aim of this study was therefore to identify objective and emotional factors that have an impact on the decision-making process. Methods: Ninety-five women with BRCA mutations or women at increased breast/ovarian cancer lifetime risk were counseled at our outpatient department and either opted for prophylactic surgery or periodic screening. To identify the psychological factors that could have influenced the decision-making, a standardized questionnaire was applied. Additionally, clinical data were collected and were reviewed by a personal talk. Results: Seventy-one of the patients opted for an increased surveillance only, 21 for prophylactic surgeries. Positive predictors for prophylactic surgeries were sociodemographic characteristics such as parity and objective variables such as verified mutation status. Hierarchical regression analysis revealed that the need for safety in health issues has been the only significant psychological predictor of surgery beyond the objective factors. Fear of surgical procedures, menopausal symptoms after surgery, loss of attractiveness, or fear of interferences with sexual life did not significantly affect decision-making. Conclusion: Decision-making towards prophylactic surgeries is influenced by objective but also emotional factors. Knowing that fear and anxiety also have an important impact on decision-making, distinct counselling about the procedures, the subsequent risk reduction as well as the psychological effects of prophylactic surgeries are essential.

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