Systemic Barriers to Risk-Reducing Interventions for Hereditary Cancer Syndromes: Implications for Health Care Inequities

Mittendorf, Kathleen F.; Knerr, Sarah; Kauffman, Tia L.; Lindberg, Nangel M.; Anderson, Katherine; Feigelson, Heather Spencer; Gilmore, Marian J.; Hunter, Jessica Ezzell; Joseph, Galen; Kraft, Stephanie A.; Zepp, Jamilyn; Syngal, Sapna; Wilfond, Benjamin S.; Goddard, Katrina A.B.

doi:10.1200/po.21.00233

Cited by 19 publications

(14 citation statements)

References 103 publications

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“…Hereditary cancer syndromes (HCS) are characterized by early‐onset, aggressive tumor development that occurs in multiple tissue types. 1 , 2 While the number of HCS is substantial, most are rare. Studies of rare HCS, such as Fanconi anemia, ataxia telangiectasia, and xeroderma pigmentosum (XP) have contributed substantially to the understanding of DNA repair mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Genetically engineered mouse models for hereditary cancer syndromes

et al. 2023

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Advances in molecular diagnostics have led to improved diagnosis and molecular understanding of hereditary cancers in the clinic. Improving the management, treatment, and potential prevention of cancers in carriers of predisposing mutations requires preclinical experimental models that reflect the key pathogenic features of the specific syndrome associated with the mutations. Numerous genetically engineered mouse (GEM) models of hereditary cancer have been developed. In this review, we describe the models of Lynch syndrome and hereditary breast and ovarian cancer syndrome, the two most common hereditary cancer predisposition syndromes. We focus on Lynch syndrome models as illustrative of the potential for using mouse models to devise improved approaches to prevention of cancer in a high‐risk population. GEM models are an invaluable tool for hereditary cancer models. Here, we review GEM models for some hereditary cancers and their potential use in cancer prevention studies.

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Section: Introductionmentioning

confidence: 99%

Genetically engineered mouse models for hereditary cancer syndromes

et al. 2023

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“…Prior studies of patient's risk management use in initiatives designed to increase access to genetic testing in healthy populations (i.e., not in the context of a disease diagnosis) have largely shown moderate to high engagement with subsequent recommended care 17–21 . However, with a few notable exceptions, these initiatives have engaged “early test adopters” and we have limited understanding of healthcare utilization patterns following cancer genetic testing in populations who traditionally face barriers in accessing genetic servies 13,22 . Whether returning genetic test results with no clear risk‐management implications, for instance variants of uncertain significance (VUS), leads to unnecessary risk management utilization due to patient anxiety or clinician mismanagement is another question of interest, particularly given health care resource constraints these populations already experience 14,23,24 …”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19][20][21] However, with a few notable exceptions, these initiatives have engaged "early test adopters" and we have limited understanding of healthcare utilization patterns following cancer genetic testing in populations who traditionally face barriers in accessing genetic servies. 13,22 Whether returning genetic test results with no clear risk-management implications, for instance variants of uncertain significance (VUS), leads to unnecessary risk management utilization due to patient…”

Section: Introductionmentioning

confidence: 99%

Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study

Guo,

Knerr,

Kauffman

et al. 2023

Cancer Medicine

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BackgroundGenetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services.MethodsCHARM was implemented in Kaiser Permanente Northwest (KPNW) and Denver Health (DH) between 2018 and 2020. We identified post‐testing screening (mammography, breast MRI, colonoscopy) and surgical (mastectomy, oophorectomy) procedures using electronic health records. We examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines.ResultsCHARM participants were followed for an average of 15.4 months (range: 0.4–27.8 months) after results disclosure. Less than 2% (11/680) received actionable risk management recommendations (i.e., could be completed in the initial years following testing) based on their test result. Among those who received actionable recommendations, risk management utilization was moderate (54.5%, 6/11 completed any procedure) and varied by procedure (mammogram: 0/3; MRI: 2/4; colonoscopy: 4/5; mastectomy: 1/5; oophorectomy: 0/3). Cancer screening and surgery procedures were rare in participants without actionable recommendations.ConclusionThough the number of participants who received actionable risk management recommendations was small, our results suggest that implementing CHARM's risk assessment and testing model increased access to evidence‐based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging risk management overuse.

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“…More specifically, ascertainment of families with LS (in which there are no premonitory lesions), the identification of PV and best-practise clinical surveillance, reduces morbidity and mortality dramatically [13][14][15]. The recommended frequency, invasiveness, and procedure-associated risks of colonoscopies (and other cancer-screening tests) are known to influence adherence and compliance to cancer-screening guidelines [16][17][18][19]. Existing screening and surveillance guidelines for LSVH are based on average age-specific cumulative cancer risk [20].…”

Section: Introductionmentioning

confidence: 99%

Immunogenomic Biomarkers for Early Cancer Detection in Lynch Syndrome

Chambuso¹,

Mthembu²,

Kaambo³

et al. 2022

Preprint

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Lynch syndrome (LS) is an inherited disorder in which affected individuals have a significantly higher-than-average risk of developing colorectal and non-colorectal cancers, often before the age of 50 years. In LS, mutations in DNA repair genes lead to a dysfunctional post-replication repair system. As a result, the unrepaired errors in coding regions of the genome produce novel proteins, called neoantigens. Neoantigens are recognised by the immune system as foreign and trigger an immune response. Due to the invasive nature of cancer screening tests, universal cancer screening guidelines unique for LS (including colonoscopy) are poorly adhered to by LS variant heterozygotes (LSVH). Currently, it is unclear whether immunogenomic components produced as a result of neoantigen formation can be used as novel biomarkers in LS. We hypothesize that: (i) LSVH produce measurable and dynamic immunogenomic components in blood, and (ii) these quantifiable immunogenomic components correlate with cancer onset and stage. Here, we discuss feasibility and propose the potential to: (a) identify personalised novel immunogenomic biomarkers, (b) reduce invasive cancer screening tests and thus increase non-invasive cancer surveillance, (c) improve compliance and adherence to recommended cancer screening guidelines in LSVH.

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Systemic Barriers to Risk-Reducing Interventions for Hereditary Cancer Syndromes: Implications for Health Care Inequities

Cited by 19 publications

References 103 publications

Genetically engineered mouse models for hereditary cancer syndromes

Genetically engineered mouse models for hereditary cancer syndromes

Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study

Immunogenomic Biomarkers for Early Cancer Detection in Lynch Syndrome

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