Variations and patterns in germline and somatic testing by age in ovarian, primary peritoneal, and fallopian tube cancer patients: a descriptive analysis in a large, real-world clinical and genetic data registry.

OBJECTIVE

To evaluate the relationship between genomic instability score and age distribution in ovarian, primary peritoneal, and fallopian tube cancers and to characterize age-related patterns in germline, homologous recombination deficiency (HRD), and somatic tumor testing using a large real-world clinical registry.

METHODS

Patients with ovarian, primary peritoneal, and fallopian tube cancers who underwent germline and/or somatic testing were identified from the Myriad Collaborative Research Registry (MCRR), version 4 (March 2025). Genomic instability scores (GIS) and tumor mutation profiles were analyzed across four age groups (<50, 50-59, 60-69, and ≥70 years). HRD positivity was defined as GIS ≥ 42. Testing patterns were evaluated by ordering specialty. Comparisons were performed using chi-square testing with significance defined as p < 0.05.

RESULTS

Among 110,119 patients with ovarian, peritoneal, or fallopian tube cancer, HRD positivity decreased with increasing age (36.2% in <50 years, 36.4% in 50-59 years, 30.9% in 60-69 years, and 24.2% in ≥70 years; p < 0.0001). Median GIS was similar across age groups but demonstrated narrower distribution ranges in older patients. Subgroup analysis of patients with intermediate GIS scores (35-41) showed increasing prevalence with advancing age. Gynecologic oncologists ordered significantly more HRD tests than medical oncologists; however, HRD positivity rates were similar between specialties. Peritoneal cancer diagnoses increased with age.

CONCLUSION

Younger patients demonstrated higher rates of HRD positivity compared to older patients despite similar median GIS distributions. These findings may have implications for biomarker-driven therapeutic selection and clinical trial generalizability, particularly in older ovarian cancer populations. Further investigation is needed to understand age-related molecular differences and optimize testing and treatment strategies across age groups.