Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort

Abstract

The detection of deleterious germline mutations in BRCA1 and BRCA2 considerably influences the clinical management of healthy and diseased carriers. Therefore, the identification of persons at risk who could uptake genetic counseling and testing is pivotal. We developed a checklist with validated criteria to improve the identification, and prospectively evaluate the incidence, of familial cancer history in 5091 breast cancer patients. The rate of 30.4% of patients at high genetic risk underpins the demand for care in risk identification and counseling. The easy-to-use instrument promotes the implementation and dissemination of risk counseling by physicians. K E Y W O R D SBRCA1, BRCA2, breast cancer, familial risk, genetic testing

Prevalence of BRCA1 and BRCA2 Mutations in Patients with Primary Ovarian Cancer – Does the German Checklist for Detecting the Risk of Hereditary Breast and Ovarian Cancer Adequately Depict the Need for Consultation?

“…For easier, everyday use, a heritability checklist was drawn up [16], with the indication for genetic briefing/counselling and testing (≥ 3 points) based on the total point value. Rhiem et al were able to show that the checklist was used successfully in breast cancer patients, with a positive correlation between the score value and prevalence of a BRCA1/2 mutation [17].…”

“…Prevalence of BRCA1/2 gene mutations in the normal population is low, at 1 : 300 – 500 8 , 9 , 10 , 11 , 12 , and is currently not yet rated as sufficient justification for unselected population analysis. Therefore, in the past, different risk-assessment strategies were developed for the detection of risk groups with a substantially higher probability (≥ 10%) of BRCA1/2 mutation 17 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 . All are based on a probability calculation for BRCA1/2 mutation being carried out for the affected person on the basis of personal/family history for breast/ovarian cancer and age at first diagnosis.…”

“…Die Prävalenz für eine BRCA1/2 -Genmutation in der Normalbevölkerung ist mit 1 : 300 – 500 8 – 12 gering und wird aktuell noch nicht als ausreichend rechtfertigend für eine unselektierte Populationsanalyse bewertet. Daher wurden in der Vergangenheit verschiedene Risk-Assessment-Strategien zur Detektion von Risikogruppen, die eine deutlich höhere Wahrscheinlichkeit (≥ 10%) für eine BRCA1/2 -Mutation tragen, entwickelt 17 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 . Allen liegt zugrunde, dass auf Basis der Eigen-/Familienanamnese für Mamma-/Ovarialkarzinom und des Alters bei Erstdiagnose eine Wahrscheinlichkeitskalkulation für eine BRCA1/2 -Mutation für die Betroffene erfolgt.…”

“…The user-friendly form of the checklist led to successful implementation in everyday clinical practice. The positive correlation of the checklist with a BRCA1/2 mutation could already be demonstrated in breast cancer patients [17]. In addition, recording of a hereditary predisposition based on this checklist is required as a quality criterion in the certification requirements of the German Cancer Society (DKG; [18,19]).…”

“…Die anwenderfreundliche Form der Checkliste führte zu einer erfolgreichen Implementierung in den klinischen Alltag. Die positive Korrelation der Checkliste mit einer BRCA1/2 -Mutation konnte an Mammakarzinompatientinnen bereits gezeigt werden 17 . Darüber hinaus wird die Erfassung einer erblichen Belastung auf Basis dieser Checkliste in den Zertifizierungsvorgaben der Deutschen Krebsgesellschaft (DKG; 18 , 19 ) als Qualitätskriterium gefordert.…”