Abstract
P2 Clinical utility of universal genetic predisposition testing in cancer patients and impact on patients with gynecologic malignancies
Gynecologic oncology, Vol.173(Supplement 1), pp.S8-S9
07/2023
DOI: 10.1016/j.ygyno.2023.05.029
Abstract
Objectives
The development of certain hereditary cancers can be attenuated or eliminated with early screening or risk-reduction interventions. For patients who undergo whole exome or whole genome testing, the American College of Medical Genomics and Genetics (ACMG) recommends reporting incidentally discovered pathogenic/likely pathogenic (P/LP) variants with highly penetrant phenotypes since these mutations have important treatment, prevention, or early disease identification strategies. The National Comprehensive Cancer Network (NCCN) recommends that all patients with epithelial ovarian and endometrial cancer under age 50 undergo germline genetic testing. The primary objective of this study is to assess the clinical utility of universal hereditary predisposition testing in cancer patients by comparing it to NCCN guideline-directed testing strategies.
Methods
Between June 2017 and January 2021, patients unselected for family history or disease site and stage enrolled in the multi-institutional Total Cancer Care prospective cohort study. Patients underwent research-grade germline whole exome sequencing to identify P/LP variants in any ACMG secondary findings v2.0 genes. A protocol modification at our institution in October 2018 permitted the return of positive research sequencing results to the clinical team. Carriers were then referred to genetic counseling for confirmatory clinical testing. We compared P/LP cases to NCCN germline testing guidelines.
Results
We enrolled 786 patients. The most frequent primary disease sites included gynecologic (182, 23%), colorectal (124, 16%), lung/bronchus (83, 11%), and head/neck (82, 10%). The median age at diagnosis was 61 (IQR 52–68) years, 57% were female, and 96% were non-Hispanic White. NCCN guideline-directed testing would have missed 61% (43/71) of the 71 mutations identified in the cohort (positive rate: 9%). Of the 182 gynecologic cancer patients, 19% (16/86) of patients with ovarian/fallopian tube, 8% (6/78) of patients with endometrial, and 6% (1/18) of patients with cervical/vulvar/vaginal carcinoma carried a mutation (Table). NCCN guideline-directed testing would have missed 21% (5/24) of these mutations. Several patients have undergone risk reduction strategies because of study participation, including a BRCA2 mutation identified and returned to a patient treated for a malignant ovarian germ cell tumor with a fertility-sparing approach. This patient has subsequently undergone prophylactic bilateral mastectomies and is under active ovarian cancer surveillance.
Conclusions
This study highlights the benefit of returning research-grade whole exome sequencing to cancer patients. Molecular testing may identify targeted cancer therapies; however, it may also identify unanticipated germline mutations. Our results suggest universal germline testing may identify patients with high-risk gene mutations otherwise missed by the standard-of-care approach.
Details
- Title: Subtitle
- P2 Clinical utility of universal genetic predisposition testing in cancer patients and impact on patients with gynecologic malignancies
- Creators
- Megan Hutchcraft - University of KentuckyShulin Zhang - University of KentuckyNan Lin - University of KentuckyRachel Miller - University of KentuckyJustine Pickarski - Markey Cancer CenterSainan Wei - University of KentuckyFrederick Ueland - University of KentuckyJill Kolesar - University of Kentucky
- Resource Type
- Abstract
- Publication Details
- Gynecologic oncology, Vol.173(Supplement 1), pp.S8-S9
- Publisher
- Elsevier Inc; SAN DIEGO
- DOI
- 10.1016/j.ygyno.2023.05.029
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Language
- English
- Date published
- 07/2023
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696543702771
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