Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers.

Purpose: To investigate frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC).

Methods: We undertook analysis in 311 women with DCIS and 392 with G1BC and extended panel testing (non-/) in 176/311 with DCIS and 156/392 with G1BC. We investigated PV detection by age at diagnosis, Manchester Score (MS), DCIS grade and receptor status.

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes: , , and .

Germline pathogenic variants (GPVs) in the cancer predisposition genes , , , , , , , and are 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 in , , , and , there are few guidelines on how to manage the more moderate OC risk in patients with GPV in , , and , with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of and R as 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.

The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in and .

Background: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO).

Methods: Our study recruited 875 female -heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO.

UK recommendations for germline genetic testing and surveillance in clinical practice.

pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history.

High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer.

Background: While the likelihood of identifying constitutional breast cancer-associated , and pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.

Methods: Sequencing of , and c.

Uptake and efficacy of bilateral risk reducing surgery in unaffected female and carriers.

Background: Women testing positive for pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy carriers.