Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene.

Purpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.

Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.

Optimization of polygenic risk scores in BRCA1/2 pathogenic variant heterozygotes in epithelial ovarian cancer.

Purpose: A third of familial epithelial ovarian cancer (EOC) is explained by BRCA1/2 pathogenic variants. Polygenic risk scores (PRSs) for BRCA1/2 heterozygotes associated with EOC have been created, but impact of combination with clinical and hormonal risk factors is unclear.

Methods: We genotyped 300 cases and 355 controls and constructed modified PRSs based on those validated by Barnes et al.

Is Reflex Germline Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour / variants. The value of germline testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour testing by the North West of England Genomic Laboratory Hub.

High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer.

Purpose: Epithelial ovarian cancer (EOC) is associated with pathogenic variants (PVs) in homologous recombination and/or mismatch repair genes. We aimed to review the testing of women with familial EOC at our center.

Methods: Women with familial EOC (≥2 EOC in family, including index case) referred to our center between 1993 and 2021 were included.

Predicting the likelihood of a pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer.

Aims: Clinical guidelines recommend testing both germline and tumour DNA for pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline PVs.

Methods: An observational study that included all tumour PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022.

BRCA1/2 in non-mucinous epithelial ovarian cancer: tumour with or without germline testing?

National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive cases of NMEOC (n = 388) to validate guidelines. Thirty-four somatic BRCA1/2 (sBRCA) PVs (9.

Dominant-negative pathogenic variant BRIP1 c.1045G>C is a high-risk allele for non-mucinous epithelial ovarian cancer: A case-control study.

BRIP1 is a moderate susceptibility epithelial ovarian cancer (EOC) gene. Having identified the BRIP1 c.1045G>C missense variant in a number of families with EOC, we aimed to investigate the frequency of this and BRIP1.

Specialist oncological surgery for removal of the ovaries and fallopian tubes in BRCA1 and BRCA2 pathogenic variant carriers may reduce primary peritoneal cancer risk to very low levels.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is highly effective for the prevention of high-grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing.

Mainstreaming germline BRCA1/2 testing in non-mucinous epithelial ovarian cancer in the North West of England.

Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics.

Epithelial ovarian cancer risk: A review of the current genetic landscape.

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies.

Adjuvant chemotherapy and outcomes in patients with nodal and resection margin-negative pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Adjuvant chemotherapy (AC) following pancreatic carcinoma (PC) resection improves overall survival (OS). A systematic review identified 10 phase-2/3 studies investigating AC in 3644 patients looking at the influence of nodal and resection status. AC significantly improved disease free survival, OS and 5-year odds of death risk.

Prevalence of germline pathogenic variants in sequential epithelial ovarian cancer cases.

Introduction: Poly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic / variant. Consequently, the demand for germline testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification.

Balancing the Economics and Ethics of Personalised Oncology.

The cost of personalised medicine in oncology is increasing. The varied and contrasting priorities of the pharmaceutical industry, local and national governments, international medical community, and patients need to be reviewed and balanced. In addition to the economic and political standpoints on this issue, the ethical considerations from physicians' viewpoints need to be considered to optimise cancer patients' care.

Everolimus in the treatment of neuroendocrine tumors of the respiratory and gastroenteropancreatic systems.

Neuroendocrine tumors (NETs) are a rare diverse group of malignancies occurring most commonly in the gastroenteropancreatic system and the lungs. The incidence of NETs is increasing worldwide; median survival for patients with metastatic NETs is 5-65 months. A growing body of evidence shows survival benefit in patients with advanced NETs (gastroenteropancreatic and lung) treated with mTOR inhibitor everolimus, with improvement in survival being demonstrated in the clinical trial and real-world setting.