High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer
| العنوان: | High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer |
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| المؤلفون: | Stephanie L Greville-Haygate, Emma R. Woodward, D. Gareth Evans, Andrew J Wallace, Helen Byers, Jamie M Ellingford, Fiona Lalloo, Anthony Howell, George J Burghel, Sasha J Howell, Miriam J. Smith, Elaine F. Harkness, William G. Newman, Naomi L. Bowers, Elke M van Veen, Diana Eccles, Sarah J Evans, Marta Pereira |
| المصدر: | Journal of Medical Genetics |
| بيانات النشر: | BMJ Publishing Group, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Adult, medicine.medical_specialty, endocrine system diseases, PALB2, Genes, BRCA2, Genes, BRCA1, human genetics, Breast Neoplasms, Disease, genetic testing, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Cancer Genetics, Medicine, Humans, genetics, Age of Onset, Prospective cohort study, skin and connective tissue diseases, CHEK2, Genetics (clinical), Genetic testing, medicine.diagnostic_test, business.industry, DNA, Neoplasm, Sequence Analysis, DNA, Ductal carcinoma, medicine.disease, Genes, p53, Checkpoint Kinase 2, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Mutation, Female, business |
| الوصف: | BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 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.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes. |
| وصف الملف: | text |
| اللغة: | English |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74b616e4efac02fce2b44a6198f63f53Test http://europepmc.org/articles/PMC8788257Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....74b616e4efac02fce2b44a6198f63f53 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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