Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

Evans, D. Gareth; Sithambaram, Siva; Veen, Elke M. van; Burghel, George J.; Schlecht, Hélene; Byers, Helen; Ellingford, Jamie M; Gandhi, Ashu; Howell, Sacha J.; Howell, Anthony; Forde, Claire; Lalloo, Fiona; Smith, Miriam J.; Woodward, Emma R

doi:10.1136/jmg-2022-108790

Cited by 4 publications

(2 citation statements)

References 21 publications

(37 reference statements)

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“…Studies of germline BRCA1/2 pathogenic variants and contralateral breast cancer risk. The systematic review of the literature identified 15 articles (13 studies [37][38][39][40][41][42][43][44][45][46][47][48][49] and two meta-analyses 50,51 ) that inform the question of whether all patients with local recurrence or contralateral primary breast cancer should be offered BRCA1/2 testing. With the exception of one study that provides direct evidence, 38 the studies identified constitute indirect evidence in support of the recommendation that BRCA1/2 testing should be offered to patients with contralateral breast cancer or ipsilateral second breast primary.…”

Section: Literature Review and Analysismentioning

confidence: 99%

Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline

Bedrosian,

Somerfield,

Achatz

et al. 2024

JCO

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PURPOSE To develop recommendations for germline mutation testing for patients with breast cancer. METHODS An ASCO–Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process. RESULTS Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations. RECOMMENDATIONS BRCA1/ 2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/ 2 testing, regardless of family history. BRCA1/ 2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/ 2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history. Additional information is available at www.asco.org/breast-cancer-guidelines .

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Section: Literature Review and Analysismentioning

confidence: 99%

Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline

Bedrosian,

Somerfield,

Achatz

et al. 2024

JCO

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“…A total of nine studies (22)(23)(24)(25)(26)(27)(28)(29)(30) presented frequencies of germline variants that allowed the following comparisons: HR-HER2+ versus TNBC (Supplementary Figure 5), HR-HER2+ versus HR+HER2-(Supplementary Figure 6), HR+HER2+ versus TNBC (Supplementary Figure 7), HR+HER2+ versus HR+HER2-(Supplementary Figure 8), and HR+HER2+ versus HR-HER2+ (Supplementary Figure 9). Moreover, eleven studies (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) allowed the comparison of HR+HER2versus TNBC (Supplementary Figure 10). For each comparison, genes were included when a variant was reported in at least two studies.…”

Section: Meta-analysis Of Germline Variants Among Bc Subtypesmentioning

confidence: 99%

Germline rare variants in HER2-positive breast cancer predisposition: a systematic review and meta-analysis

de Baumont,

Cadore,

Pedrotti

et al. 2024

Front. Oncol.

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IntroductionApproximately 10% of breast cancer (BC) cases result from hereditary causes. Genetic testing has been widely implemented in BC care to determine hereditary cancer syndromes and personalized medicine. Thus, identification of individuals carrying germline pathogenic variants could be useful to provide appropriate prophylactic or screening measures for each BC subtype, however, there are few formal recommendations for genetic testing in this sense so far. In this study, we assessed rare germline variants in a specific group of genes in order to determine the association with human epidermal growth factor 2 enriched (HER2+) BC phenotype through a systematic review and meta-analysis comparing subtypes overexpressing HER2 with other clinically recognized subtypes of BC. This review was registered with PROSPERO (ID: CRD42023447571).MethodsWe conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene.ResultsOf the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively. DiscussionOur findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.

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Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: Lower rates for 5 years post chemotherapy

Evans,

Morgan,

Crosbie

et al. 2024

Genetics in Medicine

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Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

Cited by 4 publications

References 21 publications

Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline

Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline

Germline rare variants in HER2-positive breast cancer predisposition: a systematic review and meta-analysis

Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: Lower rates for 5 years post chemotherapy

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