Germline BRCA testing in pancreatic cancer: improving awareness, timing, turnaround, and uptake

Golan, T., Casolino, R., Biankin, A. V. , Hammel, P., Whitaker, K. D., Hall, M. J. and Riegert-Johnson, D. L. (2023) Germline BRCA testing in pancreatic cancer: improving awareness, timing, turnaround, and uptake. Therapeutic Advances in Medical Oncology, (doi: 10.1177/17588359231189127) (PMID:37720496) (PMCID:PMC10504836) (Early Online Publication)

Abstract

Prognosis is generally poor for patients with pancreatic ductal adenocarcinoma. However, patients with germline BRCA1 or BRCA2 mutations (gBRCAm) may benefit from first-line platinum-based chemotherapy and maintenance therapy with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib following at least 16 weeks of first-line platinum-based chemotherapy without disease progression. Germline breast cancer gene (BRCA) testing is therefore important to ensure that patients receive the most effective treatment. In addition, testing for other DNA damage response gene mutations beyond gBRCAm may also guide treatment decisions. However, clinical pathways for genetic testing are often suboptimal, leading to delays in treatment initiation or missed opportunities for personalized therapy. Barriers to testing include low rates of referral and uptake, delays to referral and slow result turnaround times, cost, and biopsy and assay limitations if somatic testing is performed, leading to the requirement for subsequent dedicated germline testing. Low rates of referral may result from lack of awareness among physicians of the clinical value of testing, coupled with low confidence in interpreting test results and poor availability of genetic counseling services. Among patients, barriers to uptake may include similar lack of awareness of the clinical value of testing, anxiety regarding the implications of test results, lack of insurance coverage, fear of negative insurance implications, and socioeconomic factors. Potential solutions include innovative approaches to testing pathways, including ‘mainstreaming’ of testing in which BRCA tests are routinely arranged by the treating oncologist, with the involvement of genetic counselors if a patient is found to have a gBRCAm. More recently, the utility of multigene panel analyses has also been explored. Access to genetic counseling may also be improved through initiatives such as having a genetic counseling appointment for all new patient visits and telemedicine approaches, including the use of telephone consultations or DVD-assisted counseling. Educational programs will also be beneficial, and cost effectiveness is likely to improve as the number of targeted treatments increases and when the earlier detection of tumors in family members following cascade testing is considered.

• Item Type: Articles
• Additional Information: Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by AstraZeneca as part of an alliance between AstraZeneca and Merck Sharp and Dohme LLC, a subsidiary of Merck and Co., Inc., Rahway, NJ, USA, who are co-developing olaparib.
• Keywords: targeted therapy, pancreatic ductal adenocarcinoma, germline BRCA mutation, genetic counseling, genetic testing, referral.
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Biankin, Professor Andrew and Casolino, Dr Raffaella

Creator Roles

Casolino, R.: Conceptualization, Writing – review and editing
Biankin, A.: Conceptualization, Writing – review and editing

• Authors: Golan, T., Casolino, R., Biankin, A. V., Hammel, P., Whitaker, K. D., Hall, M. J., and Riegert-Johnson, D. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Therapeutic Advances in Medical Oncology
• Publisher: SAGE Publications
• ISSN: 1758-8340
• ISSN (Online): 1758-8359
• Published Online: 15 September 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Therapeutic Advances in Medical Oncology 2023
• Publisher Policy: Reproduced under a Creative Commons licence