Patterns of confirmatory germline testing in patients with somatic BRCA1/2 pathogenic variants across solid tumor types in a community oncology setting.

e23331 Background: Tumor mutation profiling serves as an essential diagnostic tool in oncology, facilitating the identification of targetable variants and informing treatment decisions. Somatic pathogenic / likely pathogenic (P/LP) variants in BRCA1 and BRCA2 (BRCA1/2) have been pivotal in guiding the use of PARP inhibitors for managing certain malignancies. Despite the established guidelines recommending germline testing upon the identification of somatic P/LP BRCA1/2 variants, adherence to confirmatory testing varies. Understanding the patterns of confirmatory germline testing across various cancer types in the community oncology setting is crucial for optimizing patient management, familial risk assessment, and treatment outcomes. Methods: This is a retrospective observational cohort study using data from electronic health records. The study population includes adult cancer patients within the US Oncology Network who underwent somatic tumor mutation profiling for solid tumors between November 1, 2021, and November 1, 2023, and were found to have a somatic P/LP BRCA1/2 variant. Descriptive analyses were conducted to evaluate patient characteristics, somatic testing results, and confirmatory germline testing rates, overall and by cancer type. Results: The study identified 526 cancer patients across participating US Oncology Network practices who had a P/LP BRCA1/2 variant identified on somatic tumor mutation profiling for solid tumors. The study population had a median age of 63 years (IQR 54 - 72) and was predominantly white (70%) across all cancer types. The three most common cancers were breast (19%), ovarian (13%), and non-small cell lung (13%). Overall, 55% of patients underwent confirmatory germline testing. Among those tested, 54% were confirmed to have germline P/LP BRCA1/2 variants (Table 1). Confirmatory testing rates were higher in BRCA1/2 associated cancers (breast, ovarian, prostate, pancreas) compared to other cancer types. Conclusions: Confirmatory germline testing remains suboptimal, particularly in cancer types less commonly associated with germline P/LP BRCA1/2 variants. This highlights the need for further education on testing in these patients. Improved awareness and adherence to testing guidelines are needed to ensure appropriate genetic risk assessment and personalized treatment strategies. Rates of confirmatory germline testing and germline BRCA1/2 positivity among the most common cancer types (n >25 patients). Patients with Somatic P/LP BRCA1/2,n (%) Overall526 Breast102 (19) Ovarian71 (13) NSCLC71 (13) Colon51 (10) Prostate35 (7) Endometrial33 (6) Pancreas28 (5) Germline Testing, n (%) 289 (55) 72 (71) 61 (86) 14 (20) 21 (41) 24 (69) 20 (61) 19 (68) Germline P/LP BRCA1/2 Confirmed, n (%) 157 (54) 49 (68) 40 (66) <10 <10 15 (62) <10 15 (79)

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Publication Details

Journal
Journal of Clinical Oncology
Published
2025-05-28
DOI
https://doi.org/10.1200/jco.2025.43.16_suppl.e23331
Primary Topic
BRCA gene mutations in cancer
Type
article
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article

Patterns of confirmatory germline testing in patients with somatic BRCA1/2 pathogenic variants across solid tumor types in a community oncology setting.

Janet L. Espirito, Molly Mendenhall, Nicole Fulcher, Kate Principe et al.
Journal of Clinical Oncology
BRCA gene mutations in cancer
article

Patterns of confirmatory germline testing in patients with somatic BRCA1/2 pathogenic variants across solid tumor types in a community oncology setting.

Janet L. Espirito, Molly Mendenhall, Nicole Fulcher, Kate Principe, Becky Clark, Shawn E. Lipinski, Kieran Hart, Siobhán O’Connor, Nino Balanchivadze, Carole Berini, Matthew Whitesell, Joanna Alyse Young, Clare Morris, Karen L. Tedesco, Barbara Kunz, Malcolm Charles, Leanne Kocemba, Shannon Southwick, Aimee Macagney
article en

Abstract

e23331 Background: Tumor mutation profiling serves as an essential diagnostic tool in oncology, facilitating the identification of targetable variants and informing treatment decisions. Somatic pathogenic / likely pathogenic (P/LP) variants in BRCA1 and BRCA2 (BRCA1/2) have been pivotal in guiding the use of PARP inhibitors for managing certain malignancies. Despite the established guidelines recommending germline testing upon the identification of somatic P/LP BRCA1/2 variants, adherence to confirmatory testing varies. Understanding the patterns of confirmatory germline testing across various cancer types in the community oncology setting is crucial for optimizing patient management, familial risk assessment, and treatment outcomes. Methods: This is a retrospective observational cohort study using data from electronic health records. The study population includes adult cancer patients within the US Oncology Network who underwent somatic tumor mutation profiling for solid tumors between November 1, 2021, and November 1, 2023, and were found to have a somatic P/LP BRCA1/2 variant. Descriptive analyses were conducted to evaluate patient characteristics, somatic testing results, and confirmatory germline testing rates, overall and by cancer type. Results: The study identified 526 cancer patients across participating US Oncology Network practices who had a P/LP BRCA1/2 variant identified on somatic tumor mutation profiling for solid tumors. The study population had a median age of 63 years (IQR 54 - 72) and was predominantly white (70%) across all cancer types. The three most common cancers were breast (19%), ovarian (13%), and non-small cell lung (13%). Overall, 55% of patients underwent confirmatory germline testing. Among those tested, 54% were confirmed to have germline P/LP BRCA1/2 variants (Table 1). Confirmatory testing rates were higher in BRCA1/2 associated cancers (breast, ovarian, prostate, pancreas) compared to other cancer types. Conclusions: Confirmatory germline testing remains suboptimal, particularly in cancer types less commonly associated with germline P/LP BRCA1/2 variants. This highlights the need for further education on testing in these patients. Improved awareness and adherence to testing guidelines are needed to ensure appropriate genetic risk assessment and personalized treatment strategies. Rates of confirmatory germline testing and germline BRCA1/2 positivity among the most common cancer types (n >25 patients). Patients with Somatic P/LP BRCA1/2,n (%) Overall526 Breast102 (19) Ovarian71 (13) NSCLC71 (13) Colon51 (10) Prostate35 (7) Endometrial33 (6) Pancreas28 (5) Germline Testing, n (%) 289 (55) 72 (71) 61 (86) 14 (20) 21 (41) 24 (69) 20 (61) 19 (68) Germline P/LP BRCA1/2 Confirmed, n (%) 157 (54) 49 (68) 40 (66) <10 <10 15 (62) <10 15 (79)

Journal of Clinical OncologyVol. 43(16_suppl)
Texas Oncology (US), Virginia Oncology Associates (US), Mountain Blue Cancer Care Center (US), Compass Oncology (US), New York Oncology Hematology (US), Virginia Cancer Specialists (US), Rocky Mountain Cancer Centers (US), Hematology Oncology Associates (US), The US Oncology Network (US), Oncology Hematology Care (US), Arizona Oncology (US), Comprehensive Cancer Centers of Nevada (US)
Openalex Percentile: Top 86%
BRCA gene mutations in cancer
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