Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2

Samuel, David; Diaz-Barbe, Alexandra; Pinto, André; Schlumbrecht, Matthew; George, Sophia

doi:10.3390/cells11030539

Cited by 17 publications

(12 citation statements)

References 102 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of individualised risk assessment was emphasised, given that only a small number of PALB2 carriers, without OC family history are likely to reach a lifetime OC risk of 5%, but if there is a family history of OC, a larger proportion of carriers will reach a lifetime risk of 5% ( There is now evidence that OC can arise from the fallopian tubes and that removal of the fallopian tubes may therefore decrease the risk of OC. [68][69][70] This raises the possibility of using salpingectomy with delayed oophorectomy to decrease OC risk while delaying surgical menopause in carriers at increased risk of OC.…”

Section: Question 18: At What Age Should Rrso Be Considered For Palb2...mentioning

confidence: 99%

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2

Hanson

Kulkarni²,

Loong³

et al. 2022

J Med Genet

View full text Add to dashboard Cite

Germline pathogenic variants (GPVs) in the cancer predisposition genesBRCA1,BRCA2,MLH1,MSH2,MSH6,BRIP1,PALB2,RAD51DandRAD51Care identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV inBRCA1,BRCA2,MLH1,MSH2andMSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV inBRIP1,PALB2,RAD51DandRAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition ofRAD51Cand RAD51Das OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management ofBRIP1,PALB2,RAD51DandRAD51Ccarriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.

show abstract

Section: Question 18: At What Age Should Rrso Be Considered For Palb2...mentioning

confidence: 99%

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2

Hanson

Kulkarni²,

Loong³

et al. 2022

J Med Genet

View full text Add to dashboard Cite

show abstract

“…For all BRCA mutation carriers, a 3.5% cumulative risk for peritoneal cancer after prophylactic oophorectomy was reported after 20 years of follow-up ( 38 ). One STIC patient had a PALB2 gene mutation which is also involved in hereditary breast and ovarian cancer but insufficiently determines the ovarian cancer risk ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature

et al. 2022

View full text Add to dashboard Cite

ObjectiveSerous tubal intraepithelial carcinoma (STIC) is a precursor lesion of pelvic high-grade serous carcinoma (HGSC). Information on treatment and outcome of isolated STIC is rare. Therefore, we reviewed systematically the published literature to determine the incidence of subsequent HGSC in the high- and low-risk population and to summarize the current diagnostic and therapeutic options.MethodsA systematic review of the literature was conducted in MEDLINE-Ovid, Cochrane Library and Web of Science of articles published from February 2006 to July 2021. Patients with an isolated STIC diagnosis and clinical follow-up were included. Study exclusion criteria for review were the presence of synchronous gynaecological cancer and/or concurrent non-gynaecological malignancies.Results3031 abstracts were screened. 112 isolated STIC patients out of 21 publications were included in our analysis with a pooled median follow-up of 36 (interquartile range (IQR): 25.3-84) months. 71.4% of the patients had peritoneal washings (negative: 62.5%, positive: 8%, atypic cells: 0.9%). Surgical staging was performed in 28.6% of all STICs and did not show any malignancies. 14 out of 112 (12.5%) patients received adjuvant chemotherapy with Carboplatin and Paclitaxel. Eight (7.1%) patients developed a recurrence 42.5 (IQR: 33-72) months after isolated STIC diagnosis. Cumulative incidence of HGSC after five (ten) years was 10.5% (21.6%). Recurrence occurred only in BRCA1 carriers (seven out of eight patients, one patient with unknown BRCA status).ConclusionThe rate of HGSC after an isolated STIC diagnosis was 7.1% with a cumulative incidence of 10.5% (21.6%) after five (ten) years. HGSC was only observed in BRCA1 carriers. The role of adjuvant therapy and routine surveillance remains unclear, however, intense surveillance up to ten years is necessary.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021278340.

show abstract

“…For example, in BRCA1 - and BRCA2 -associated hereditary breast and ovarian cancer syndromes (HBOC), RRSO decreases the incidence of EOC and reduces mortality [ 32 , 33 , 34 , 35 ], whereas the potential benefits and dangers of oral contraceptive pills, a type of chemoprophylaxis for EOC, remain unclear [ 36 ]. In contrast to the high-penetrance BRCA1 or BRCA2 ( BRCA1/2 ) gene, there is still substantial controversy regarding the degree of conferred risks for EOC in individuals with other EOC predisposition genes and whether those risks are sufficiently elevated above the general population to warrant consideration of RRSO [ 37 , 38 ]. Additionally, RRSO has potential negative aspects with regard to women’s health, such as cardiovascular events and osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

“…Even though RRSO prevents EOC, there is concern that cardiovascular events caused by RRSO-induced ovarian dysfunction may worsen life expectancy and reduce the quality of life due to menopausal symptoms. For this reason, several clinical trials are currently being conducted to demonstrate the risk-reducing effects of prior risk-reducing salpingectomy (RRS) [ 38 , 39 , 40 , 41 ]. Because most EOC-associated genes are involved in one of two DNA repair pathways [ 42 ], a fundamental understanding of disease drivers in these pathways will allow us to accurately estimate the genetic risk of developing EOC and select appropriate prevention and treatment strategies for hereditary EOC.…”

Section: Introductionmentioning

confidence: 99%

Moderate-Risk Genes for Hereditary Ovarian Cancers Involved in the Homologous Recombination Repair Pathway

Abe

Imoto

Ueki

et al. 2022

IJMS

View full text Add to dashboard Cite

Approximately 20% of cases of epithelial ovarian cancer (EOC) are hereditary, sharing many causative genes with breast cancer. The lower frequency of EOC compared to breast cancer makes it challenging to estimate absolute or relative risk and verify the efficacy of risk-reducing surgery in individuals harboring germline pathogenic variants (GPV) in EOC predisposition genes, particularly those with relatively low penetrance. Here, we review the molecular features and hereditary tumor risk associated with several moderate-penetrance genes in EOC that are involved in the homologous recombination repair pathway, i.e., ATM, BRIP1, NBN, PALB2, and RAD51C/D. Understanding the molecular mechanisms underlying the expression and function of these genes may elucidate trends in the development and progression of hereditary tumors, including EOC. A fundamental understanding of the genes driving EOC can help us accurately estimate the genetic risk of developing EOC and select appropriate prevention and treatment strategies for hereditary EOC. Therefore, we summarize the functions of the candidate predisposition genes for EOC and discuss the clinical management of individuals carrying GPV in these genes.

show abstract

Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2

Cited by 17 publications

References 102 publications

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2

Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature

Moderate-Risk Genes for Hereditary Ovarian Cancers Involved in the Homologous Recombination Repair Pathway

Contact Info

Product

Resources

About