Screening Familial Risk for Hereditary Breast and Ovarian Cancer

• Published in: JAMA network open 2024-09, Vol.7 (9), p.e2435901
• Main Authors: Kiser, Daniel, Elhanan, Gai, Bolze, Alexandre, Neveux, Iva, Schlauch, Karen A, Metcalf, William J, Cirulli, Elizabeth T, McCarthy, Catherine, Greenberg, Leslie A, Grime, Savanna, Blitstein, Jamie M Schnell, Plauth, William, Grzymski, Joseph J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Cross-Sectional Studies; Electronic health records; Family medical history; Fanconi Anemia Complementation Group N Protein; Female; Females; Genetic Predisposition to Disease; Genetic testing; Genetic Testing - methods; Genetic Testing - statistics & numerical data; Genetics and Genomics; Hereditary Breast and Ovarian Cancer Syndrome - diagnosis; Hereditary Breast and Ovarian Cancer Syndrome - epidemiology; Hereditary Breast and Ovarian Cancer Syndrome - genetics; Humans; Male; Middle Aged; Nevada - epidemiology; Online Only; Original Investigation; Ovarian cancer; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Patients; Retrospective Studies; Young Adult
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2024.35901

Most patients with pathogenic or likely pathogenic (P/LP) variants for breast cancer have not undergone genetic testing. To identify patients meeting family history criteria for genetic testing in the electronic health record (EHR). This study included both cross-sectional (observation date, February 1, 2024) and retrospective cohort (observation period, January 1, 2018, to February 1, 2024) analyses. Participants included patients aged 18 to 79 years enrolled in Renown Health, a large health system in Northern Nevada. Genotype was known for 38 003 patients enrolled in Healthy Nevada Project (HNP), a population genomics study. An EHR indicating that a patient is positive for criteria according to the Seven-Question Family History Questionnaire (hereafter, FHS7 positive) assessing familial risk for hereditary breast and ovarian cancer (HBOC). The primary outcomes were the presence of P/LP variants in the ATM, BRCA1, BRCA2, CHEK2, or PALB2 genes (cross-sectional analysis) or a diagnosis of cancer (cohort analysis). Age-adjusted cancer incidence rates per 100 000 patients per year were calculated using the 2020 US population as the standard. Hazard ratios (HRs) for cancer attributable to FHS7-positive status were estimated using cause-specific hazard models. Among 835 727 patients, 423 393 (50.7%) were female and 29 913 (3.6%) were FHS7 positive. Among those who were FHS7 positive, 24 535 (82.0%) had no evidence of prior genetic testing for HBOC in their EHR. Being FHS7 positive was associated with increased prevalence of P/LP variants in BRCA1/BRCA2 (odds ratio [OR], 3.34; 95% CI, 2.48-4.47), CHEK2 (OR, 1.62; 95% CI, 1.05-2.43), and PALB2 (OR, 2.84; 95% CI, 1.23-6.16) among HNP female individuals, and in BRCA1/BRCA2 (OR, 3.35; 95% CI, 1.93-5.56) among HNP male individuals. Being FHS7 positive was also associated with significantly increased risk of cancer among 131 622 non-HNP female individuals (HR, 1.44; 95% CI, 1.22-1.70) but not among 114 982 non-HNP male individuals (HR, 1.11; 95% CI, 0.87-1.42). Among 1527 HNP survey respondents, 352 of 383 EHR-FHS7 positive patients (91.9%) were survey-FHS7 positive, but only 352 of 883 survey-FHS7 positive patients (39.9%) were EHR-FHS7 positive. Of the 29 913 FHS7-positive patients, 19 764 (66.1%) were identified only after parsing free-text family history comments. Socioeconomic differences were also observed between EHR-FHS7-negative and EHR-FHS7-positive patients, suggesting disparities in recording family histor