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Article
Open AccessLow-level constitutional mosaicism of BRCA1 in two women with young onset ovarian cancer
Germline pathogenic variants in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer. The vast majority of these variants are inherited from a parent. De novo constitutional pathogenic variants are rare. Ev...
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Article
Open AccessCurrent recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group
The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, misc...
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Article
Open AccessCurrent recommendations for cancer surveillance in Gorlin syndrome: a report from the SIOPE host genome working group (SIOPE HGWG)
Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum o...
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Article
Neurofibromatosis type 2 discordance in monozygous twins
Neurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in the NF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the pr...
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Article
Global Disparities in Breast Cancer Genetics Testing, Counselling and Management
Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5–10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validate...
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Article
Low Lifetime Risk of Contralateral Breast Cancer in a Middle-Income Asian Country: Evidence to Guide Post-treatment Surveillance
The rate of contralateral risk-reducing mastectomy (CRRM) is increasing in the West with controversial evidence of improved survival in early breast cancer patients. Although uptake of CRRM in Asia appears low...
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Article
Spinal ependymomas in NF2: a surgical disease?
The management of spinal cord ependymomas in Neurofibromatosis Type 2 (NF2) has traditionally been conservative, in contrast to the management of sporadic cases; the assumption being that, in the context of NF...
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Article
Open AccessHomozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD)
Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations hav...
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Article
Open AccessRisk algorithms that include pathology adjustment for HER2 amplification need to make further downward adjustments in likelihood scores
To assess the need for adjustment in the likelihood of germline BRCA1/2 mutations in women with HER2+ breast cancers. We analysed primary mutation screens on women with breast cancer with unequivocal HER2 overexp...
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Article
Open AccessIntensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality
The addition of annual MRI screening to mammography has heightened optimism that intensive screening along with improved treatments may substantially improve life expectancy of women at high risk of breast can...
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Article
Open AccessA heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening
Childhood meningiomas are rare. Recently, a new hereditary tumor predisposition syndrome has been discovered, resulting in an increased risk for spinal and intracranial clear cell meningiomas (CCMs) in young p...
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Article
Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens
The aim of this study is to delineate more clearly the prevalence of HER2+ breast cancer in women with germline BRCA1/2 mutations. For this purpose, we analysed primary mutation screens on women with breast cance...
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Article
Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis
BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk facto...
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Article
Open AccessThe Manchester guidelines for contralateral risk-reducing mastectomy
Rates of contralateral risk-reducing mastectomy (CRRM) are rising, despite a decreasing global incidence of contralateral breast cancer. Reasons for requesting this procedure are complex, and we have previousl...
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Article
Open AccessUptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic
Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention ...
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Article
Mammographic surveillance in women aged 35–39 at enhanced familial risk of breast cancer (FH02)
Although there have been encouraging recent studies showing a potential benefit from annual mammography in women aged 40–49 years of age with an elevated breast cancer risk due to family history there is littl...
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Article
Open AccessDistribution of breast cancer risk from SNPs and classical risk factors in women of routine screening age in the UK
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Article
The spectrum of urological malignancy in Lynch syndrome
Urological tumours are the third most frequent malignancy in Lynch syndrome after colonic and endometrial cancer. Upper urinary tract tumours are well recognised in Lynch syndrome, but the association with pro...
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Article
Open AccessAssociation of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study
The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methyle...
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Article
Open AccessBRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years
Triple-negative (TN) tumours are the predominant breast cancer subtype in BRCA1 mutation carriers. Recently, it was proposed that all individuals below 50 years of age with TN breast cancer should be offered BRCA...
