Family history criteria used to predict breast cancer genetic risk variants
In a recent study, patients with a positive response to the Seven-Question Family History Questionnaire were more likely to present with a pathogenic or likely pathogenic variant in the BRCA1 and BRCA2 genes.
Family history criteria used to predict breast cancer genetic risk variants | Image Credit: © okrasiuk - © okrasiuk - stock.adobe.com.
Patients with a familial risk of breast cancer can be identified using the electronic health record (EHR)-derived Seven-Question Family History Questionnaire (FHS7), according to a recent study published in JAMA Network Open.1
Data has indicated up to 80% of patients with a pathogenic or likely pathogenic (P/LP) variant in the BRCA1 and BRCA2 (BRCA1/2) genes lack knowledge of their condition and are at increased risk of hereditary breast and ovarian cancer (HBOC). Additionally, the odds of identifying rare or less penetrant P/LP variants are further reduced.2
Women with P/LP variants in BRCA1/2 have a lifetime breast cancer risk over 50%, making early population-wide genetic testing vital.1 To address the gap in genetic testing, the US Preventive Services Task Force (USPSTF) recommends the use of family history tools such as the FHS7.
Investigators conducted a study to determine the patients with family history criteria for genetic testing based on EHR derived FHS7. Eligibility criteria included being aged 18 to 79 years, not deceased, and with at least 1 recorded personal or family history assessment.
Relevant data included demographic and health care variables, HBOC-related cancer diagnoses, evidence of previous HBOC-related genetic testing, and dates of death. International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify diagnoses.
EHRs were assessed for family history of HBOC-cancers by combining discrete codes and string matches in the comment field. USPSTF eligibility was determined based on meeting any 1 of the 7 FHS7 criteria.
In the cross-sectional analysis, investigators evaluated whether considering a personal history of relevant cancers alongside EHR-derived FHS7 criteria improved accuracy. Participants in the cohort analysis were grouped based on biological sex.
Of participants, 54.7% were aged under 50 years and 50.7% were female. Additionally, 8.8% had a family history of at least 1 HBOC-related cancer in their EHRs and 3.6% were FHS7 positive. Of relatives identified with HBOC-related cancers, 70.6% would have remained unidentified if the text comments went ignored, alongside 66.1% FHS7-positive patients.
The most common positive responses were derived from the fifth and seventh FHS7 questions. Patients with a positive FHS7 result were less likely to be aged under 50 years, Hispanic, and live in a low-income Census tract, with odds ratios (ORs) of 0.43, 0.50, and 0.60, respectively.
FHS7-positive patients were also more often female and White, with ORs of 2.70 and 1.95, respectively. These patients had a higher rate of health care utilization, with a difference of $12,105 vs FHS7-negative patients.
A 3-fold increased risk of being BRCA1/2 positive was reported in both male and female patients with FHS7-positive status. When prescreening with FHS7, the number needed to test to detect a BRCA1/2-positive patient decreased from 128 to 53 among women and from 119 to 42 among men.
The cohort analysis included 131,622 female individuals and 114,982 male individuals, 4.7% and 2%, respectively, of whom were FHS7-positive. Cancer development occurred in 1.6% and 1.9%, respectively.
When adjusting for age, the cancer incidence rates were 239.3 cases per 100,000 per year among FHS7-negative female patients vs 367.2 cases per 100,000 per year among FHS7-positive female patients. These rates were 260.1 cases per 100,000 per year and 309.9 cases per 100,000 per year, respectively, among male patients.
These results indicated a significant association between family history criteria and genetic risk variants for HBOC. Investigators concluded implementation of a direct FHS7 questionnaire would improve detection of patients with HBOC.
References
- Kiser D, Elhanan G, Bolze A, et al. Screening familial risk for hereditary breast and ovarian cancer. JAMA Netw Open. 2024;7(9):e2435901. doi:10.1001/jamanetworkopen.2024.35901
- Wood ME, McKinnon W, Garber J. Risk for breast cancer and management of unaffected individuals with non-BRCA hereditary breast cancer.Breast J. 2020;26(8):1528-1534. doi:10.1111/tbj.13969
