학술논문
Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients
Document Type
article
Author
Whitney Espinel; Marjan Champine; Heather Hampel; Joanne Jeter; Kevin Sweet; Robert Pilarski; Rachel Pearlman; Kate Shane; Pamela Brock; Judith A. Westman; Lindsay Kipnis; Jilliane Sotelo; Anu Chittenden; Samantha Culver; Jill E. Stopfer; Katherine A. Schneider; Rosalba Sacca; Diane R. Koeller; Shraddha Gaonkar; Erica Vaccari; Sarah Kane; Scott T. Michalski; Shan Yang; Sarah M. Nielsen; Sara L. Bristow; Stephen E. Lincoln; Robert L. Nussbaum; Edward D. Esplin
Source
Cancers, Vol 14, Iss 10, p 2426 (2022)
Subject
Language
English
ISSN
2072-6694
Abstract
Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients’ family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.