Germline genetic profiles of women with ovarian malignancies: A Myriad Collaborative Research Registry study.
Authors: Aryasomayajula Chinmayi , Johnson Caitlin Ruth , Francoeur Alex Andrea , Stewart Chelsea , Kapp Daniel Stuart , Chan John K 
Published: June 2024

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Background: To compare the characteristics and genetic mutational profiles of patients with ovarian, fallopian tube and primary peritoneal cancers by age and self-identified ancestry. Methods: Data on patients with epithelial ovarian, fallopian, and peritoneal cancers who had germline, MyChoice, and/or Precise testing were obtained from the Myriad Collaborative Research Registry. Gene mutations of interest were obtained from TAPUR studies currently under enrollment. Graph Pad Prism v10.1.1 was utilized for statistical calculations. Results: Of 96,149 patients with ovarian, fallopian tube, and peritoneal cancers, 32.6% were diagnosed between the age of 0-49 and 67.4% were diagnosed aged ≥50. In this cohort, 65.0% identified as Non-Hispanic White (NHW), 6.9% as Hispanic, 5.1% as Non-Hispanic Black (NHB), 3.4% as Non-Hispanic Asian/Pacific Islander (NHAPI), and 19.6% as other/unspecified. Of this population, 33.6% of patients in the younger cohort and 66.4% of patients in the older cohort had germline genetic mutations. Of the identified germline mutations, 63.6% were found in NHW, 10.5% in NHB, 9.0% in Hispanic, and 5.9% in NHAPI. Additionally, 15.1% of patients had germline mutations associated with hereditary ovarian cancer. Of these, 22.5% were in BRCA1, 16.6% were in BRCA2, and 8.2% were in Lynch associated genes. Furthermore, 39.4%, 34.1%, and 25.9% of patients with ovarian, fallopian tube, and primary peritoneal cancers harbored BRCA mutations, respectively. Of patients with germline mutations, BRCA mutations were noted in 44.9% of younger patients and 38.4% of older patients. Based on race, 40.5%, 39.8%, 31.4%, and 22.0% of NHW, Hispanic, NHAPI, and NHB patients were BRCA+ with access to PARP-inhibitors. Younger women had more HRD positivity than older women (37.8% vs 30.9%; p<0.0001). Regarding race, HRD positivity was higher in NHAPI (40.9%) and Hispanics (39.4%) than NHB (31.6%) and NHW (29.0%) women (p<0.0001). Mutations in Lynch genes were detected in 9.6% patients in the younger cohort and 7.5% of patients in the older cohort (p<0.0001). Lynch mutations were detected in 9.4% of NHAPI patients, 8.6% of NHW, 6.8% of NHB, and 6.5% of Hispanics (p<0.0001). There were no differences in CDK4 (p=0.6), PTEN (p=0.3), or p53 (p=0.2) mutations among various racial groups. Of all tested patients, 65.0% were NHW, 6.9% were Hispanic, 5.1% were NHB, and 3.4% were NHAPI. Specifically, a significantly higher proportion of NHW patients received both germline (68.8%) and tumor testing (37.5%) compared to testing rates for all other racial groups (<10%; p<0.0001). Conclusions: Based on this large registry, our data showed that over 15% of patients with ovarian malignancies have mutations in BRCA (12.5%) or Lynch genes (2.6%) with varying prevalence by race, age, and tumor site. Noted disparities indicate the importance of universal testing in patients with epithelial ovarian malignancies.