New surveillance guidelines for Li-Fraumeni and hereditary TP53 related cancer syndrome: implications for germline TP53 testing in breast cancer

Evans, D. Gareth; Woodward, Emma R.

doi:10.1007/s10689-020-00207-z

Cited by 8 publications

(7 citation statements)

References 49 publications

(102 reference statements)

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“…It is notable that the detection of 2000 index cases in the MCGM has led to the subsequent identification of over 3000 positive family members, who can then benefit from cancer prevention and early detection strategies. Where genetic testing is undertaken in wider settings rather than a dedicated genetics clinic, accurate variant classification will be critical [ 33 ], along with attention to possible mosaicism [ 34 ] and appropriate clinical management being put in place, especially where potentially discordant clinical features and germline CPG variants are detected.…”

Section: Discussionmentioning

confidence: 99%

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

et al. 2021

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It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990–2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.

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Section: Discussionmentioning

confidence: 99%

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

et al. 2021

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“…Normally, ME is discussed in order to avoid breast radiation after BCS due to the risk of radiationinduced secondary malignancies, such as sarcoma, small lung cancer or thyroid cancer, which is described in up to 33% of individuals with LFS. 22,23,[25][26][27] Furthermore, the risk of in-breast recurrence after radiation has been addressed previously by Heymann et al, who found an ipsilateral "in-field relapse" of BC in three out of six patients after a median follow-up of 6 years. 23 A recent study by Le et al with a follow-up of 12.5 years described a lower risk for locoregional BC recurrence in the chest wall after post-ME radiotherapy (n = 1/8, 13%) and for secondary malignancies (sarcomas: n = 1/18, 6%; thyroid cancer: n = 1/18, 6%) and pointed out that there is no absolute contraindication for radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“… 22 , 23 , 24 , 25 Mastectomy (ME) and contralateral prophylactic mastectomy (CPM) might be options to prevent local BC recurrence or contralateral BC. 17 , 22 , 26 , 27 There is little evidence about surgical approaches, prophylactic operations (PO) and LFS‐specific BC characteristics besides the described high frequency of HER2‐amplified BC subtypes. 15 , 25 , 28 , 29 , 30 , 31 , 32 To date, LFS is not addressed concretely in the German BC S3 guideline.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer characteristics and surgery among women with Li‐Fraumeni syndrome in Germany—A retrospective cohort study

et al. 2021

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“…Nonetheless, mutations in TP53 may account for almost as many breast cancers in patients ≤30 years of age as BRCA2 [36], and diagnosis at an age ≤30 years is a criterion for testing by the Chompret criteria [37]. Overall, 2–8% of breast cancers in patients aged ≤30 years harbor a TP53 germline PV and these are more common with HER2+ invasive disease and high-grade comedo-DCIS [38]. Detection rates drop dramatically after 30 years of age, and testing of women after age 45 years with no previous malignancy and no other element of Chompret criteria fulfilled (no typical Li-Fraumeni cancer in a close relative) is not recommended [37].…”

Section: Molecular Geneticsmentioning

confidence: 99%

From BRCA1 to Polygenic Risk Scores: Mutation-Associated Risks in Breast Cancer-Related Genes

2021

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Background: There has been huge progress over the last 30 years in identifying the familial component of breast cancer. Summary: Currently around 20% is explained by the high-risk genes BRCA1 and BRCA2, a further 2% by other high-penetrance genes, and around 5% by the moderate risk genes ATM and CHEK2. In contrast, the more than 300 low-penetrance single-nucleotide polymorphisms (SNP) now account for around 28% and they are predicted to account for most of the remaining 45% yet to be found. Even for high-risk genes which confer a 40–90% risk of breast cancer, these SNP can substantially affect the level of breast cancer risk. Indeed, the strength of family history and hormonal and reproductive factors is very important in assessing risk even for a BRCA carrier. The risks of contralateral breast cancer are also affected by SNP as well as by the presence of high or moderate risk genes. Genetic testing using gene panels is now commonplace. Key-Messages: There is a need for a more parsimonious approach to panels only testing those genes with a definite 2-fold increased risk and only testing those genes with challenging management implications, such as CDH1 and TP53, when there is strong clinical indication to do so. Testing of SNP alongside genes is likely to provide a more accurate risk assessment.

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New surveillance guidelines for Li-Fraumeni and hereditary TP53 related cancer syndrome: implications for germline TP53 testing in breast cancer

Cited by 8 publications

References 49 publications

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

Breast cancer characteristics and surgery among women with Li‐Fraumeni syndrome in Germany—A retrospective cohort study

From <b><i>BRCA1</i></b> to Polygenic Risk Scores: Mutation-Associated Risks in Breast Cancer-Related Genes

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