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High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer
- Source :
- Journal of Medical Genetics
- Publication Year :
- 2021
- Publisher :
- BMJ Publishing Group, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14686244 and 00222593
- Volume :
- 59
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics
- Accession number :
- edsair.doi.dedup.....74b616e4efac02fce2b44a6198f63f53