Limited Independent Follow-Up with Germline Testing of Variants Detected in BRCA1 and BRCA2 by Tumor-Only Sequencing

Carol J. Nowlen, Molly Daniels, Burak Uzunparmak, Ecaterina E. Ileana Dumbrava, Ying Yuan, Keyur P. Patel, Nadine Rayes, Jacqueline Harkenrider, Chetna Wathoo, Jennifer Veazie, Krystle A. Luna, Wanlin Wang, Chacha Horombe, Milind Javle, Jordi Rodon Ahnert, Timothy A. Yap, Banu Arun, Karen H. Lu, Funda Meric-Bernstam

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients. Methods: A retrospective chart review was performed to identify patients with BRCA1/2 variants on tumor-only genomic profiling, and whether they had germline testing. Results: This study found that of 2923 patients with 36 tumor types who underwent tumor-only testing, 554 had a variant in BRCA1/2 (19.0%); 119 of the 554 patients (21.5%) had a P/LP BRCA1/2 variant, representing 4.1% of the overall population who underwent genomic profiling. Seventy-three (61.3%) of 119 patients with BRCA1/2 P/LPV on tumor-only testing did not undergo germline testing, 34 (28.6%) had already had germline testing before tumor-only testing, and 12 (10.1%) underwent germline testing after tumor-only testing. Twenty-eight germline BRCA1/2 P/LPVs were detected, 24 in those who had prior germline testing, and 4 among the 12 patients who had germline testing after tumor-only testing. Conclusion: Tumor-only testing is likely to identify P/LPVs in BRCA1/2. Efforts to improve follow-up germline testing is needed to improve identification of germline BRCA1/2 alterations.

Original languageEnglish (US)
Pages (from-to)7-17
Number of pages11
JournalJournal of Immunotherapy and Precision Oncology
Volume7
Issue number1
DOIs
StatePublished - Feb 2024

Keywords

  • BRCA1
  • BRCA2
  • germline testing
  • tumor-only testing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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