Experience of urologists, oncologists and nurse practitioners with mainstream genetic testing in metastatic prostate cancer.

Background: International guidelines recommend germline genetic testing for men with metastatic prostate cancer. If offered to all patients by genetic healthcare professionals, there will be insufficient capacity to cope with the high patient numbers. In a mainstreaming pathway, non-genetic healthcare professionals (ngHCPs) discuss and order germline genetic testing instead of referring patients to genetic healthcare professionals.

Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families.

Purpose: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported.

Optimizing the detection of hereditary predisposition in women with epithelial ovarian cancer: nationwide implementation of the Tumor-First workflow.

Genetic testing in patients with ovarian carcinoma (OC) is crucial, as around 10-15% of these women have a genetic predisposition to OC. Although guidelines have recommended universal germline testing for all patients with OC for a decade, implementation has proved challenging, thus resulting in low germline-testing rates (around 30-50%). Many new initiatives to improve genetic-testing rates have emerged, but most have been carried out at the local level, leading to differences in workflows within and between countries.

Long-term outcome of high-grade serous carcinoma established in risk-reducing salpingo-oophorectomy specimens in asymptomatic BRCA1/2 germline pathogenic variant carriers.

Objective: The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing salpingo-oophorectomy (RRSO) specimen.

Methods: In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS).

Men with metastatic prostate cancer carrying a pathogenic germline variant in breast cancer genes: disclosure of genetic test results to relatives.

Some patients with metastatic prostate cancer carry a pathogenic germline variant (PV) in a gene, that is mainly associated with an increased risk of breast cancer in women. If they test positive for such a PV, prostate cancer patients are encouraged to disclose the genetic test result to relatives who are at risk in case the carrier status changes the relatives' medical care. Our study aimed to investigate how men who learned they carry a PV in BRCA1, BRCA2, PALB2, CHEK2 or ATM disclosed their carrier status to at-risk relatives and to assess the possible psychological burden for the carrier and their perception of the burden for relatives.

Information Provision Regarding Health-Related Direct-to-Consumer Genetic Testing for Dutch Consumers: An in-Depth Content Analysis of Sellers' Websites.

: Previous studies have suggested that information offered by sellers of health-related direct-to-consumer genetic tests (DTC-GTs) is often incomplete, unbalanced, or too difficult to understand. The extent to which this is the case for sellers accessible to Dutch consumers has not previously been studied. : The present study aimed to assess the completeness, balance, readability, and findability of informational content on a selection of websites from several health-related DTC-GT sellers accessible to Dutch consumers.

Urinary incontinence more than 15 years after premenopausal risk-reducing salpingo-oophorectomy: a multicentre cross-sectional study.

Objective: To study the impact of premenopausal risk-reducing salpingo-oophorectomy (RRSO), compared with postmenopausal RRSO, on urinary incontinence (UI) ≥10 years later.

Design: Cross-sectional study, nested in a nationwide cohort.

Setting: Multicentre in the Netherlands.

Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation.

Background: Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA-associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1/2-associated BC.

Methods: The gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study.

The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer: Tumor-First or Germline-First?

Objective: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing.

Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk.

Background And Aims: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs.

Methods: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs.

High-Grade Serous Carcinoma at Risk-Reducing Salpingo-Oophorectomy in Asymptomatic Carriers of Pathogenic Variants: Prevalence and Clinical Factors.

Purpose: To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic -pathogenic variant (PV) carriers.

Patients And Methods: We included -PV carriers who underwent RRSO between 1995 and 2018 from the Hereditary Breast and Ovarian cancer in the Netherlands study. All pathology reports were screened, and histopathology reviews were performed for RRSO specimens with epithelial abnormalities or where HGSC developed after normal RRSO.

Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on cognition in women with high familial risk of ovarian cancer: A cross-sectional study.

Objective: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO.

Design: A cross-sectional study with prospective follow-up, nested in a nationwide cohort.

Setting: Multicentre in the Netherlands.

[Oncogenetics].

Determining whether a hereditary cancer predisposition is present, is important for both the cancer patient and his family. It is relevant for surveillance and prevention or early detection of new tumours, treatment options and issues surrounding the desire to have children. For this reason, it must be ensured that for every patient with cancer (now or in the past) referral for genetic testing is considered.

Mainstream germline genetic testing in men with metastatic prostate cancer: design and protocol for a multicenter observational study.

Background: In international guidelines, germline genetic testing is recommended for patients with metastatic prostate cancer. Before undergoing germline genetic testing, these patients should receive pre-test counseling. In the standard genetic care pathway, pre-test counseling is provided by a healthcare professional of a genetics department.

Sexual functioning more than 15 years after premenopausal risk-reducing salpingo-oophorectomy.

Background: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a premenopausal oophorectomy. However, the long-term effects of premenopausal oophorectomy on sexual functioning are unknown.

Uncovering the Contribution of Moderate-Penetrance Susceptibility Genes to Breast Cancer by Whole-Exome Sequencing and Targeted Enrichment Sequencing of Candidate Genes in Women of European Ancestry.

Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced.