Lieke Lanjouw

BRCA1/2 testing rates in epithelial ovarian cancer: a focus on the untested patients

Since 2015, Dutch guidelines have recommended To evaluate A consecutive series of 250 patients diagnosed with epithelial ovarian cancer between 2016 and 2019 was included from the OncoLifeS data-biobank of the University Medical Center Groningen, the Netherlands. Testing rates were analyzed for the overall study population and for germline testing (period I) and tumor-first testing (period II) separately. Characteristics of tested and untested patients were compared and predictors for receiving testing were assessed with multivariable logistic regression. Median age was 67.0 years (IQR 59.0-73.0) and 173 (69.2%) patients were diagnosed with high-grade serous carcinoma. Overall, 201 (80.4%) patients were tested. In period I, 137/171 (80.1%) patients were tested and in period II this was 64/79 (81.0%). Patients with non-high-grade serous carcinoma were significantly less likely to receive The results show that

Clinicopathological Characteristics of Ovarian and Breast Cancer in PALB2, RAD51C, and RAD51D Germline Pathogenic Variant Carriers

Background/Objectives: Germline pathogenic variants (GPVs) in PALB2, RAD51C, and RAD51D increase breast cancer (BC) and ovarian cancer (OC) risk. Limited data on clinicopathological characteristics of BC and OC in women with these GPVs hamper guideline development. Therefore, this study aims to describe these characteristics in a consecutive series of female PALB2, RAD51C, and RAD51D GPV carriers. Methods: Women with a PALB2, RAD51C, or RAD51D GPV determined before July 2023 at the University Medical Center Groningen were included. Cancer diagnoses were obtained through linkage with the Dutch Nationwide Pathology Databank (Palga). Median onset age and histopathological subtypes were compared to the data of The Netherlands Cancer Registry (NCR). Results: Among 164 GPV carriers (125 PALB2, 30 RAD51C, and 9 RAD51D), 54 BC and 6 OC cases were identified. The median BC onset age was 52 (n = 50), 71 (n = 3), and 43 years (n = 1) for PALB2, RAD51C, and RAD51D, respectively, compared with 62 years in the NCR. No BC histological subtype differences were observed in PALB2 carriers. The populations of RAD51C and RAD51D carriers were too small to compare to NCR data. No OC cases occurred in PALB2 carriers. The median OC onset age was 66 (n = 4) and 56 years (n = 2) for RAD51C and RAD51D carriers, respectively, versus 67 years in the NCR. All RAD51D carriers had high-grade serous carcinoma, compared to 51.5% in the NCR. Conclusions: Differences in onset age and histological subtypes were observed between GPV carriers and national data. Further research on cancer characteristics is needed to optimize counseling and cancer prevention in these women.

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.