Understanding the Clinical Implications of Low Penetrant Genes and Breast Cancer Risk

Vaidyanathan, Anusha; Kaklamani, Virginia

doi:10.1007/s11864-021-00887-4

Cited by 6 publications

(4 citation statements)

References 51 publications

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“… 1 To target high-risk variants, genetic testing guidelines developed by professional organizations are largely determined by age at diagnosis and personal and/or family history. 2 Additionally, risk assessment tools such as the BRCAPRO statistical model use a patient’s personal cancer status and family history to assist in recommendation for genetic testing. 3 Germline testing for BRCA1 , BRCA2 ( BRCA1/2 ), CDH1 , PALB2 , PTEN , and TP53 is currently recommended for certain patients with breast cancer by the National Comprehensive Cancer Network (NCCN) guidelines; however, studies of universal testing with multigene panels suggest that guidelines should be broadened to include testing of all individuals with solid tumors and include genes beyond those with proven breast cancer associations.…”

Section: Introductionmentioning

confidence: 99%

“…The value of identifying patients with highly penetrant, pathogenic or likely pathogenic germline genetic variants (PGVs) in clinical management for cancer predisposition has been well-established . To target high-risk variants, genetic testing guidelines developed by professional organizations are largely determined by age at diagnosis and personal and/or family history . Additionally, risk assessment tools such as the BRCAPRO statistical model use a patient’s personal cancer status and family history to assist in recommendation for genetic testing .…”

Section: Introductionmentioning

confidence: 99%

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Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

et al. 2022

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ImportanceNational Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration.ObjectiveTo examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making.Design, Setting, and ParticipantsPatients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022.ExposureNew and/or previous diagnosis of breast cancer.Main Outcomes and MeasuresDisease management recommendations that were changed as a result of genetic testing results are reported.ResultsClinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]).Conclusions and RelevanceIn this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

et al. 2022

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“…The severity and the type of breast cancer highly depend on the types of the gene mutated, as each gene corresponds to the development of different types of cancer as discussed in Table 1. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] The analysis of breast cancer risk for the BRCA mutated population is depicted in Figure 1.…”

Section: Risk Factors Of Gene Mutationmentioning

confidence: 99%

Genetic Contribution to Breast Cancer: A Critical Analysis of Penetrance Alleles as Susceptible Genes

Kaur,

Singh

2023

J Explor Res Pharmacol

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Breast cancer can develop either in the tubes connecting the lobules of milk-producing glands to the nipple or the lobules themselves. GLOBOCAN 2021 reported an estimated 14.1 million new instances of cancer, 8.2 million cancer-related deaths, and 32.6 million people who had cancer for at least five years after their diagnosis. The development of genomic instability enables the acquisition of functional cells to become cancerous allowing the survival, proliferation, and dissemination of malignancy. These cells develop distinctive abilities as a result of acquired rare genetic mutations. Multistep tumor growth is caused by a succession of clonal expansions that are set off by the accidental discovery of an enabling mutant genotype. Hence, it is vital to identify defective genes in breast cancer and breast cancer therapy to mitigate the need for treatment. Critical analyses of various defective genes are compiled in this review.

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“…Evidence regarding low penetrance BC susceptibility genes comes mostly from small case series; their association with BC continues to be a matter of debate, and risk estimates need to be better defined. Table 3 summarizes recent data published on this topic [24 ▪ ,31 ▪ ,32].…”

Section: Low Penetrance Breast Cancer-susceptibility Genesmentioning

confidence: 99%

Local treatment in patients with hereditary breast cancer: decision-making process in low-, moderate-, high-penetrance pathogenic germline mutation carriers

Sibilio

Curcio

Toesca

et al. 2022

Current Opinion in Oncology

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Purpose of reviewWe summarize recent evidence regarding commonly tested breast cancer susceptibility genes and review indications derived from recently published guidelines regarding management of carriers affected by early breast cancer (BC).Recent findingsManagement of affected women with a known genetic predisposition to BC was matter of debate at the most relevant international conferences, such as St. Gallen International Consensus Conference and San Antonio Breast Cancer Symposium held both in 2021. At the same time, a joint Experts Panel from American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology (ASCO/ASTRO/SSO) convened to develop recommendations to support clinical decision-making in this specific setting and results about administration of new systemic therapies such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors became available.SummaryPopulation of patients affected by BC and carriers of mutations in susceptibility genes is progressively increasing, but new mutations identified do not always have a clear clinical impact.To date, we have data to support consideration of different local management choices for affected patients carrying specific mutations, but some issues especially relating to breast-conserving surgery or administration of radiotherapy in these patients, still need to be better addressed. Opinions about the best way to treat these patients are still heterogeneous and information deriving from different sources seems to be conflicting at times. Our purpose is to offer a synopsis of the different evidence available that may be helpful in clinical decision making.

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Understanding the Clinical Implications of Low Penetrant Genes and Breast Cancer Risk

Cited by 6 publications

References 51 publications

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

Genetic Contribution to Breast Cancer: A Critical Analysis of Penetrance Alleles as Susceptible Genes

Local treatment in patients with hereditary breast cancer: decision-making process in low-, moderate-, high-penetrance pathogenic germline mutation carriers

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