A systematic review and meta-analysis of germline BRCA mutations in pancreatic cancer patients identifies global and racial disparities in access to genetic testing

Paiella, Salvatore; Azzolina, Danila; Gregori, Darío; Malleo, Giuseppe; Golan, Talia; Simeone, Diane M.; Davis, Micheal; Vacca, Paola; Crovetto, A; Bassi, Claudio; Salvia, Roberto; Biankin, Andrew V.; Casolino, Raffaella

doi:10.1016/j.esmoop.2023.100881

Cited by 9 publications

(4 citation statements)

References 108 publications

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“…This is critical step in improving access and addressing known cancer health disparities in ethnic minorities. [23][24][25][26][27] A future direction for this work is a collaboration with the provincial cancer registry to implement a real-time systematic clinician prompt for mainstreaming testing at the time of pathology confirmation. Another area is to increase cascade testing uptake rate, which was low in our study at only 15.2% of all potentially eligible individuals for an overall ratio of 0.56 relatives tested per index case.…”

Section: Discussionmentioning

confidence: 99%

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma

Cremin,

Bedard,

Hong

et al. 2024

JCO Precis Oncol

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PURPOSE Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic–initiated testing (HCT) pathway and a new oncology clinic–initiated testing (OCT) pathway. METHODS Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes. RESULTS The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease ( P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group ( P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306). CONCLUSION The real-world observations in our study show that oncology clinic–initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma

Cremin,

Bedard,

Hong

et al. 2024

JCO Precis Oncol

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“…The evidence on which testing recommendations are based is often biased toward White non-Hispanic populations. 112,113 Fewer Asian, Black, and Hispanic individuals receive germline genetic testing. 95 Because of this undertesting, interpretation of identified variants in these populations leads to a higher frequency of VUS results.…”

Section: Health Disparitiesmentioning

confidence: 99%

Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline

Tung,

Ricker,

Messersmith

et al. 2024

JCO

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ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases, or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 ( online only) for more. PURPOSE To guide use of multigene panels for germline genetic testing for patients with cancer. METHODS An ASCO Expert Panel convened to develop recommendations on the basis of a systematic review of guidelines, consensus statements, and studies of germline and somatic genetic testing. RESULTS Fifty-two guidelines and consensus statements met eligibility criteria for the primary search; 14 studies were identified for Clinical Question 4. RECOMMENDATIONS Patients should have a family history taken and recorded that includes details of cancers in first- and second-degree relatives and the patient's ethnicity. When more than one gene is relevant based on personal and/or family history, multigene panel testing should be offered. When considering what genes to include in the panel, the minimal panel should include the more strongly recommended genes from Table 1 and may include those less strongly recommended. A broader panel may be ordered when the potential benefits are clearly identified, and the potential harms from uncertain results should be mitigated. Patients who meet criteria for germline genetic testing should be offered germline testing regardless of results from tumor testing. Patients who would not normally be offered germline genetic testing based on personal and/or family history criteria but who have a pathogenic or likely pathogenic variant identified by tumor testing in a gene listed in Table 2 under the outlined circumstances should be offered germline testing. Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines .

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“…This is consistent with observation that PARP inhibitor Olaparib does improve progression-free survival when used as a maintenance therapy in the subgroup of patients with metastatic PDAC and a BRCA1/-2 germ line mutation, that bene t from platinum-based chemotherapy [26]. Such evidence represented a clear indication that the BRCA1/-2 mutational status should be routinely investigated in metastatic PDACthough the expected occurrence of mutations in these genes for this malignancy is lower than 4% (any BRCA mutation: 3.3%; 1.7-5.3% [27]) within the Caucasian/white population.…”

Section: Introductionmentioning

confidence: 99%

Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population

Sini,

Doro,

Frogheri

et al. 2024

Preprint

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Background Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia. Methods A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms. Results Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival. Conclusions The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.

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A systematic review and meta-analysis of germline BRCA mutations in pancreatic cancer patients identifies global and racial disparities in access to genetic testing

Cited by 9 publications

References 108 publications

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma

Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline

Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population

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