According to data being presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, the use of upfront multi-gene panel testing (MGPT) in patients with endometrial cancer has led to an improvement in Lynch syndrome (LS) diagnoses among this population.

There has been a marked increase in the use of upfront germline genetic testing to identify hereditary syndromes and aid in the treatment of patients with cancer. Experts opine that such testing should be considered for patients with any and all solid tumors, including endometrial cancer.

“Although tumor-based screening is highly effective, some LS diagnoses will be missed. Upfront [MGPT] for endometrial cancer has been evaluated as an alternative approach to identifying LS with the potential to simultaneously find actionable germline variants in other cancer susceptibility genes (CSGs),” wrote lead investigator Monica Levine, MD, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, and colleagues.

Thus, Dr Levine et al conducted a study to define the frequency and types of actionable germline variants in a large, unselected group of patients with endometrial cancer.

A total of 961 patients with endometrial cancer diagnosed between 2017 and 2020 were enrolled at 9 institutions, and clinicopathologic data were abstracted from the patients’ records. The investigators performed prospective germline MGPT for 47 CSGs.

The investigators identified 101 likely pathogenic (LP) or pathogenic variants (PV) in 98 (10.2%) patients. The most common were LP/PVs in LS genes, and 29 (3.02%) LS cases were identified (95% CI, 2.1-4.3%).

MGPT led to the detection of 9 LS cases not identified by tumor screening, including 6 in patients from institutions that do not perform tumor screening and 3 who had normal immunohistochemistry.

Furthermore, 72 LP/PVs were found in 17 different CSGs; 21 (2.1%) patients had LP/PVs in high penetrance CSGs other than the LS genes, 19 of which were in genes tied to breast and/or ovarian cancer (4 in BRCA1, 6 in BRCA2, 6 in BRIP1, 2 in PALB2, 1 in RAD51C).

Of note, BRCA1/2 PVs (1.04% of the total study population, 95% CI 0.6-1.9%) were significantly more common in patients with type II cancers than in the rest of the cohort (P = .005, hazard ratio, 2.00; 95% CI, 1.16-4.75). There were 21 additional LP/PVs found in moderate-risk CSGs (ATM, CHEK2, NBN, NF1).

“Upfront MGPT in an unselected endometrial cancer population improved LS diagnosis and identified an additional 2% of patients with LP/PVs in highly penetrant CSGs,” the researchers reported.

“Knowing germline status at the time of diagnosis facilitates further delineation of germline/phenotype associations, and it defines a genetic syndrome allowing for cancer prevention,” Dr Levine et al reported.

“Upfront MGPT in EC provides clinically impactful information and should be adopted into routine clinical care,” they concluded.—Hina Porcelli

Levine M, Pearlman R, Hampel H, et al. High prevalence of actionable germline variants in unselected endometrial cancer (EC) patients. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 5577.