Germline TP53 Testing in Breast Cancers: Why, When and How?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Interpretation of Germline TP53 Variants
2.1. Disease-Causing Variants
2.2. Mosaic Variants Versus Clonal Haematopoiesis and Circulating Tumour DNA
3. Cancer Risk Associated with Germline Disease-Causing TP53 Variants
4. Features of Breast Tumours in TP53 Variant Carriers
4.1. Age of Tumour-Onset
4.2. Histopathologic Features
5. Treatment-Related Risks in TP53 Variant Carriers
6. Surveillance Protocols in Carriers of Germline Disease-Causing TP53 Variants
7. Impact of a Germline Disease-Causing TP53 Variant on Genetic Counselling
8. Psychological Considerations
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ACMG | American College of Medical Genetics and Genomics |
AMP | Association for Molecular Pathology |
DCIS | ductal carcinoma in situ |
ERN | European Reference Network |
GENTURIS | Genetic tumour risk syndromes |
hTP53rc | heritable TP53-related cancer |
LFS | Li-Fraumeni syndrome |
WBMRI | Whole-Body MRI |
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Presentation | Criteria |
---|---|
Familial presentation | Patient with a TP53 core tumour (breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumour, adrenocortical carcinoma) before 46 years AND at least one first- or second-degree relative with a core tumour before 56 years |
Multiple primitive tumours | Patient with multiple tumours, including 2 TP53 core tumours, the first of which occurred before 46 years, irrespective of family history |
Rare tumours | Patient with adrenocortical carcinoma, choroid plexus carcinoma, or rhabdomyosarcoma of embryonal anaplastic subtype, irrespective of family history |
Very early-onset breast cancer | Breast cancer before 31 years, irrespective of family history |
Exam | Periodicity | Age to Start | Age to End | Condition |
---|---|---|---|---|
Clinical examination | Every six months | Birth | 17 years | |
Annual | 18 years | - | ||
Whole-Body MRI without gadolinium enhancement | Annual | Birth | - | TP53 variant conferring high cancer risk in childhood * |
18 years | - | |||
Breast MRI | Annual | 20 years | Until 65 years | |
Brain MRI ** | Annual | Birth | 18 years | TP53 variant conferring high cancer risk in childhood |
18 years | Until 50 years | |||
Abdominal ultrasound | Every six months | Birth | Until 18 years | |
Urine steroids | Every six months | Birth | Until 18 years | When abdominal ultrasound does not allow a proper imaging of the adrenal glands |
Colonoscopy | Every five years | 18 years | - | Only if the carrier received abdominal radiotherapy for the treatment of a previous cancer or if there is a familial history of colorectal tumours suggestive of an increased genetic risk |
Age of Breast Tumour Onset | Presentation |
---|---|
When TP53 testing should systematically be performed | |
Before 31 | Invasive breast carcinoma a or ductal carcinoma in situ (DCIS) |
Before 36 |
|
Before 46 |
|
When TP53 testing may be offered | |
Before 46 |
|
When TP53 testing should not be performed | |
After 46 | No previous TP53 core tumour before 46 and no familial history fulfilling Chompret criteria |
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Evans, D.G.; Woodward, E.R.; Bajalica-Lagercrantz, S.; Oliveira, C.; Frebourg, T. Germline TP53 Testing in Breast Cancers: Why, When and How? Cancers 2020, 12, 3762. https://doi.org/10.3390/cancers12123762
Evans DG, Woodward ER, Bajalica-Lagercrantz S, Oliveira C, Frebourg T. Germline TP53 Testing in Breast Cancers: Why, When and How? Cancers. 2020; 12(12):3762. https://doi.org/10.3390/cancers12123762
Chicago/Turabian StyleEvans, D. Gareth, Emma R. Woodward, Svetlana Bajalica-Lagercrantz, Carla Oliveira, and Thierry Frebourg. 2020. "Germline TP53 Testing in Breast Cancers: Why, When and How?" Cancers 12, no. 12: 3762. https://doi.org/10.3390/cancers12123762