Publications by authors named "Hoogerbrugge N"

(1) Background/Objectives: Women with hamartoma tumor syndrome (PHTS) face a significantly increased risk of breast cancer (up to 66%) and a high prevalence of benign breast lesions (30-75%), which can complicate cancer detection and underscore the need for effective surveillance strategies. This study aimed to evaluate the imaging characteristics of breast cancers and benign breast lesions using magnetic resonance imaging (MRI) and mammography, with the goal of improving early cancer detection, reducing unnecessary biopsies, and guiding future surveillance protocols. (2) Methods: This retrospective single-institution study included 65 PHTS women aged ≥18 years (2001-2021), 39 of whom participated in a high-risk breast cancer surveillance program.

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The development of multiple primary tumors is one of the hallmarks of hereditary cancer. The phenotypic presentation of individuals with multiple primary tumors is often heterogeneous, which hampers the establishment of a genetic diagnosis. The absence of a genetic diagnosis may lead to inappropriate surveillance advices and treatment choices.

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Purpose: PTEN hamartoma tumour syndrome (PHTS) is an autosomal dominant cancer-predisposition and overgrowth syndrome occurring due to pathogenic germline variants in the PTEN gene, with an increased risk of both benign and malignant tumours involving the breast, colon, endometrium, thyroid, skin, and kidney. The objective of these clinical guidelines was to use the latest knowledge to generate an international consensus resource for providers, researchers, and individuals with PHTS on the best practices in the surveillance and management of cancer and overgrowth in PHTS.

Experimental Design: The International PHTS Cancer and Overgrowth Guidelines Working Group was established, comprising a core group of six international experts in the diagnosis and management of PHTS.

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Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

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Objective: To compare menopause-related quality of life (QoL) after risk-reducing salpingectomy (RRS) versus risk-reducing salpingo-oophorectomy (RRSO) until 3 years of post-surgery.

Design: A prospective study (TUBA study) with treatment allocation based on patients' preference. Data were collected pre-surgery and at 3 months, 1 and 3 years of post-surgery.

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Article Synopsis
  • The study evaluates strategies for colorectal cancer (CRC) surveillance in individuals with familial CRC risk, comparing different methods of colonoscopy and fecal testing.
  • The optimal strategy identified is a combination of 10-yearly colonoscopy and 2-yearly FIT from ages 40 to 80, which enhances life quality and reduces costs.
  • This approach not only prevents more CRC deaths but also significantly decreases the number of colonoscopies required compared to current guidelines.
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Objective: Children with PTEN hamartoma tumor syndrome (PHTS) are at increased risk for developing thyroid abnormalities, including differentiated thyroid carcinoma (DTC). The Dutch PHTS guideline recommends ultrasound surveillance starting from age 18. Since the literature describes PHTS patients who developed DTC before age 18, the Dutch PHTS expertise centre has initiated annual ultrasound surveillance starting from age 12.

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  • The study investigates immune dysregulation in patients with PTEN Hamartoma Tumour Syndrome (PHTS) by comparing infection and autoimmune disease rates in 81 pediatric and 109 adult PHTS patients to 73 female adult controls.
  • Pediatric PHTS patients reported low rates of infections and autoimmune disease, while adult patients had significantly higher instances of viral infections, bacterial infections, and autoimmune conditions compared to the control group.
  • Findings suggest that adult PHTS patients experience a more extensive range of immune-related issues, indicated by frequent infections and a higher prevalence of autoimmune diseases.
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  • * Key findings show high odds ratios and frequencies of PVs for BRCA1, BRCA2, and PALB2, particularly in estrogen receptor-positive breast cancer, while PV frequencies for some syndromic BCSGs like TP53 and STK11 are notably low.
  • * This analysis provides valuable insights for understanding the genetic risks associated with breast cancer in the general population, which can aid in better testing and prevention strategies.
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Background: Individuals with germline pathogenic variants in BRCA1 or BRCA2 are at a high risk of breast and ovarian carcinomas with BRCA1/2 deficiency and homologous recombination deficiency that can be detected by analysis of genome-wide genomic instability features such as large-scale state transitions, telomeric allelic imbalances, and genomic loss of heterozygosity. Malignancies with homologous recombination deficiency are more sensitive to platinum-based therapies and poly(ADP-ribose) polymerase inhibitors. We investigated the fraction of non-breast or ovarian malignancies that have BRCA1/2 deficiency and genomic instability features.

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  • In biomedical research for rare diseases, model organisms are essential for understanding disease mechanisms, identifying biomarkers, and developing therapies.
  • Solve-RD is an EU-funded project focused on addressing numerous previously unresolved rare diseases.
  • The project has led to the creation of the European Rare Disease Models & Mechanisms Network (RDMM-Europe) to enhance research efforts in this area.
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PTEN hamartoma tumor syndrome (PHTS) has a broad clinical spectrum including various benign and malignant tumors at varying age of diagnosis. Many patients remain unrecognized, unaware of their increased cancer risk. We aimed to describe the cancer spectrum, age of onset and histopathological cancer characteristics to assess whether specific cancer characteristics could improve PHTS recognition.

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  • CHEK2 plays a role in homologous recombination repair (HRR) and individuals with harmful variants in this gene are at higher risk for developing breast cancer and potentially other cancers.
  • PARP inhibitors (PARPi) are effective for cancers with HRR deficiencies, such as those caused by BRCA1/2 mutations, but they have shown little success in treating cancers linked to CHEK2 variants.
  • Research indicates that cancers from individuals with biallelic CHEK2 variants do not exhibit traits associated with HRR deficiency, explaining the lack of efficacy of PARPi treatment for these patients.
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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.

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  • * Out of 40 participants, 80% exhibited average intelligence levels, but notable deficits were found in immediate memory recall (30% below average) and information processing speed (24% below average).
  • * Psychological assessments showed that approximately 25% experienced significant distress, with personality traits including inflexibility and social withdrawal, indicating a need for tailored care strategies for adults with PHTS.
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  • * A study evaluated the oral characteristics of 81 pediatric and 86 adult PHTS patients, finding that adults commonly exhibited oral features like gingival hypertrophy, oral papillomas, and high palate, with nearly all showing at least two oral signs.
  • * Dental professionals play a key role in spotting these oral manifestations, which can prompt early clinical assessments and genetic testing, potentially improving outcomes and life expectancy for patients and their families.
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Females with PTEN Hamartoma Tumor Syndrome (PHTS) have breast cancer risks up to 76%. This study assessed associations between breast cancer and lifestyle in European female adult PHTS patients. Data were collected via patient questionnaires (July 2020-March 2023) and genetic diagnoses from medical files.

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Purpose: Females with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies.

Methods: Exome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.

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  • Thyroid cancer surveillance (TCS) using ultrasound (US) is recommended for patients with PTEN hamartoma tumor syndrome (PHTS) due to their increased risk of thyroid cancer, but evidence for TCS guidelines is limited.
  • A study analyzed the effectiveness of annual TCS against less frequent screenings (biennial and triennial) in adults with PHTS over 279 follow-up years, finding multiple nodules in 87% of patients and cancer in 7%.
  • The study suggests starting TCS before age 18 and possibly shifting to biennial follow-ups after two initial US screenings if no concerning findings are present.
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Background: Germline CDH1 pathogenic or likely pathogenic variants cause hereditary diffuse gastric cancer (HDGC). Once a genetic cause is identified, stomachs' and breasts' surveillance and/or prophylactic surgery is offered to asymptomatic CDH1 carriers, which is life-saving. Herein, we characterized an inherited mechanism responsible for extremely early-onset gastric cancer and atypical HDGC high penetrance.

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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.

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Objective: Expert-opinion based guidelines state that endometrial cancer surveillance (ECS) might be considered for patients with PTEN Hamartoma Tumor Syndrome (PHTS) based on an elevated lifetime risk of endometrial cancer. We aimed to evaluate the yield of ECS by annual transvaginal ultrasound (TVUS) and endometrial biopsy (EMB) in PHTS patients.

Methods: PHTS patients who visited our PHTS expert center between August 2012 and September 2020 and opted for annual ECS were included.

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Background: Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics.

Methods: We retrieved the full tumor history of a historical clinic-based cohort of 1745 individuals with Lynch syndrome and calculated the standardized incidence ratio for all tumor types.

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The new 'Tumor-First' workflow for genetic testing in epithelial ovarian cancer detects women with a genetic predisposition effectively and efficiently. 'Tumor-First' indicates that the tumor DNA of all patients diagnosed with epithelial ovarian cancer is examined for the presence of pathogenic variants in, amongst others, BRCA1 and BRCA2 genes. Women with an aberrant tumor DNA test result are eligible for genetic testing using a sample of blood to detect heredity.

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