Coronary Artery Calcium Scores After Prophylactic Premenopausal Bilateral Salpingo-Oophorectomy.

Background: Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at high familial risk of ovarian cancer leads to immediate menopause. Although early natural menopause is associated with increased cardiovascular disease risk, evidence on long-term cardiovascular disease risk after early surgical menopause is scarce.

Objectives: We sought to determine the long-term influence of the timing of RRSO on the development of coronary artery calcium (CAC), an established marker for cardiovascular disease risk.

Low-dose aspirin prophylaxis to prevent hypertensive disorders of pregnancy after in vitro fertilisation: a scoping review protocol.

Introduction: Pregnancies resulting from in vitro fertilisation are associated with an increased risk of developing hypertensive disorders of pregnancy, such as preeclampsia, when compared with naturally conceived pregnancies.

Objective: The efficacy of aspirin prophylaxis to reduce the incidence of preeclampsia is well established in naturally conceived pregnancies identified as high risk for developing preeclampsia. However, the efficacy of aspirin to reduce the rate of preeclampsia for all pregnancies resulting from in vitro fertilisation remains uncertain, although in vitro fertilisation conception is a well-known risk factor for preeclampsia.

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).

The benefit of adding polygenic risk scores, lifestyle factors, and breast density to family history and genetic status for breast cancer risk and surveillance classification of unaffected women from germline CHEK2 c.1100delC families.

To determine the changes in surveillance category by adding a polygenic risk score based on 311 breast cancer (BC)-associated variants (PRS), questionnaire-based risk factors and breast density on personalized BC risk in unaffected women from Dutch CHEK2 c.1100delC families. In total, 117 unaffected women (58 heterozygotes and 59 non-carriers) from CHEK2 families were included.

Impact of Assisted Reproduction Techniques on Adverse Maternal Outcomes and on the Rate of Hospitalization in Maternal Intensive Care.

The aim of this retrospective cohort study is to evaluate the impact of assisted reproductive treatment (ART) on adverse maternal outcomes and the rate of hospitalization in maternal intensive care (MIC) in a tertiary university center in Liege, Belgium. This is a retrospective cohort study comparing two groups, 6557 patients who achieved pregnancy spontaneously and 330 patients who achieved pregnancy after ART, between January 2020 and December 2022. These patients were followed in the academic obstetrics department of Citadelle Hospital, Liège.

[Etiology of preeclampsia after assisted reproductive treatments].

About 12 percent of women require assisted reproductive technology (ART) to get pregnant as infertility concerns more and more couples. Recent studies highlight obstetrical complications after ART such as preeclampsia, gestational diabetes or placenta accrete spectrum. Pre-eclampsia is a specific pathology of the pregnancy which can lead to materno-fetal complications including prematurity and intrauterine growth restriction.

[Mental health of children conceived after assisted reproductive treatment].

The prevalence of infertility and the use of assisted reproductive treatment (ART) have been increasing worldwide in recent years. It appeared relevant to conduct a literature review on the safety of these techniques regarding the neurodevelopment and mental health of children and adolescents especially after in vitro fertilization. ART represents obstetrical risk factors.

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.

Breast cancer genomes from CHEK2 c.1100delC mutation carriers lack somatic TP53 mutations and display a unique structural variant size distribution profile.

Background: CHEK2 c.1100delC was the first moderate-risk breast cancer (BC) susceptibility allele discovered. Despite several genomic, transcriptomic and functional studies, however, it is still unclear how exactly CHEK2 c.

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.

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.

Rare germline copy number variants (CNVs) and breast cancer risk.

Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

Background: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.

Methods: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.

Polycystic ovarian syndrome and infertility: overview and insights of the putative treatments.

Infertility concerns 15% of the couples. Management of female infertility requires a complete history of the patient followed by a physical, gynecological and endocrine examination. Infertility etiology will be investigated thanks to different tests including ovarian function and reserve assessment, search for uterine abnormalities and evaluation of tubal permeability.

The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.

Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS and CBC risk.

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium.

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands.

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one.

Publisher Correction: Shared heritability and functional enrichment across six solid cancers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.

Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants.