Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

Background: The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.

Aim: To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.

Methods: We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020. Data was collected and analyzed on Excel sheet.

Results: In total, 358 individuals were included, including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer. The prevalence of breast cancer susceptibility gene (BRCA) 1/2 pathogenic variants was 8.63% (19/220) in patients with breast cancer, and 15.1% (5/33) in those with ovarian cancer. Among the 25 of 220 patients with breast cancer tested by next-generation sequencing, 3 patients had pathogenic variants other than BRCA1/2. The highest risk was observed in those aged 40 years with breast cancer and a positive family history, where the BRCA1/2 prevalence was 20.1% (9/43). Among the unaffected subjects, 31.1% (14/45) had the same BRCA1/2 pathogenic variants in their corresponding relatives. Among the subjects referred because of a positive family history of cancer without known hereditary factors, 5.35% (3/56) had pathogenic variants of BRCA1 and BRCA2. The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.

Conclusion: This study showed a 8.63% prevalence of pathogenic variants in patients with breast cancer and a 15.1% prevalence in patients with ovarian cancer. Among the relatives of patients with BRCA1/2 pathogenic variants, 31% tested positive for the same variant, while 5.3% of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.