Evaluation of BRCA1/2 testing rates in epithelial ovarian cancer patients: lessons learned from real-world clinical data

Abstract

Identification of somatic and germline BRCA1/2 pathogenic variants in epithelial ovarian cancer (EOC) patients is essential for determining poly-(ADP-ribose)-polymerase (PARP) inhibitor sensitivity and genetic predisposition. In the Netherlands, BRCA1/2 testing changed to a tumor-first approach to efficiently identify both somatic and germline pathogenic variants in all patients. Here, we performed an in-depth evaluation of the first four years of the tumor-first test-pathway. Data of consecutive series of patients diagnosed with EOC in two regions were obtained from the Netherlands Cancer Registry. Tumor and/or germline test data were retrieved from hospital databases. The primary outcome was the percentage of patients completing the BRCA1/2 test-pathway, defined as having a negative tumor test or a referral for a germline test in case of a positive tumor test or no tumor test. Factors associated with test-pathway completion were identified through multivariable logistic regression analysis. In total, 69.8% (757/1085) completed the test-pathway. This was 74.4% in the most recent year. Younger patients, patients diagnosed in year three or four, patients with high-grade serous/high-grade endometrioid carcinoma, advanced stage disease, middle or high socioeconomic status, and patients who underwent surgery or chemotherapy, were more likely to complete the test-pathway. We report inequalities in genetic testing access in EOC patients, which highlight the need for better guideline adherence, particularly in older patients, those with low socioeconomic status, low-grade histotypes, early-stage disease and those without surgery or chemotherapy. Additionally, timely testing of patients, and testing relatives if patients cannot be tested, are crucial to increase test uptake.

Keywords: BRCA1/2; Evaluation; Genetic predisposition; Ovarian cancer; Tumor test.

Fig. 1

Flowchart of tumor-first workflow as evaluated in the current study For every patient with a negative tumor test (i.e., no pathogenic variant in the tumor), the test-pathway was considered to be completed, and the patient’s germline status was considered to be known (e.g., BRCA1/2 wildtype). If the tumor test was positive (i.e., pathogenic variant in the tumor) or unsuccessful, it was evaluated whether the patient received a referral to Genetics, indicating the completion of the test-pathway, and if subsequently a germline test was performed, the germline status of the patient was considered to be known. ¹ Requested by pathologist (if patient has not declined the test) and performed by laboratory specialist in specialized gynecologic oncology centers. ² Gynecologist or medical oncologist refers patient if indicated. Referrals before EOC diagnosis and referrals for children of patient were included. Abbreviations: EOC, epithelial tubal/ovarian cancer; PV, pathogenic variant

Fig. 2

The percentage of patients who completed the BRCA1/2 test-pathway, in years of the tumor-first workflow