Ovarian Cancer Liquid Biopsy for Early Assessment & Detection in Individuals With BRCA1/2 Pathogenic Variants

This is a prospective, multi-center, mixed-methods feasibility study evaluating the integration of the Galleri multi-cancer early detection (MCED) liquid biopsy into hereditary cancer risk management for individuals at increased risk of epithelial ovarian cancer due to pathogenic or likely pathogenic BRCA1 or BRCA2 variants. The study also includes individuals with a prior diagnosis of serous tubal intraepithelial carcinoma (STIC), a precursor lesion associated with an increased risk of subsequent ovarian, fallopian tube, or primary peritoneal cancer.

The primary objective is to evaluate the feasibility of incorporating liquid biopsy testing into clinical care. Secondary objectives include evaluating participant acceptability, identifying barriers and facilitators to implementation, and generating preliminary data to inform a future large-scale validation study. Exploratory analyses will evaluate the relationship between liquid biopsy results and surgical pathology findings, including estimates of sensitivity, specificity, positive predictive value, negative predictive value, and concordance when feasible.

The study consists of two cohorts:

Cohort A (Surgical Feasibility Cohort):

Approximately 50 adults with BRCA1 or BRCA2 pathogenic variants who are undergoing planned risk-reducing gynecologic surgery at Weill Cornell Medicine or MD Anderson Cancer Center will receive the Galleri blood test on the day of surgery. Liquid biopsy results will be compared with surgical pathology findings to evaluate the feasibility of integrating blood-based cancer detection into hereditary cancer prevention. Participants will remain on their planned standard-of-care clinical pathway, and no additional surgical procedures will be performed for research purposes.

Cohort B (Exploratory STIC Cohort):

Up to 20 adults with a previous diagnosis of STIC will undergo baseline and annual Galleri blood testing for up to 10 years. The study will evaluate the feasibility and acceptability of long-term blood-based surveillance and descriptively characterize longitudinal liquid biopsy findings and clinical outcomes.

A subset of approximately 20-30 participants from Cohort A will complete semi-structured interviews or focus groups within six months of surgery. Interviews will be guided by Levesque's Healthcare Access Framework to explore participant perceptions, trust, barriers, facilitators, and implementation considerations related to liquid biopsy testing. Findings will help inform equitable implementation of future ovarian cancer early detection strategies.

The Galleri test used in this study is an investigational in vitro diagnostic device performed in a CLIA-certified laboratory. It is not approved by the U.S. Food and Drug Administration for ovarian cancer screening or this specific indication and is being evaluated for research purposes only.

Results from this feasibility study are intended to support the development of a future multi-site validation study evaluating the diagnostic performance of liquid biopsy for early detection of epithelial ovarian cancer in individuals with hereditary cancer susceptibility.

Inclusion criteria

Cohort A participants must meet all of the following criteria:

• Age ≥ 35 years (based on current National Comprehensive Cancer Network guidelines35 for risk-reducing gynecologic surgery) with no upper age limit
• Confirmed germline PV or likely PV in the BRCA1 or BRCA2 genes, documented by CLIA-certified genetic testing.
• Scheduled to undergo risk-reducing gynecologic surgery (salpingo-oophorectomy or salpingectomy with or without hysterectomy) at the study site.
• Willing and able to provide informed consent in English This initial phase is limited to English-speaking participants. This limitation is due to feasibility considerations for initial qualitative instrument validation; future phases will incorporate translated materials

Cohort B participants must meet all of the following criteria:

• Age ≥ 35 years with no upper age limit.
• STIC lesion previously identified on surgical pathology within the prior 10 years.
• Willing and able to undergo baseline and annual research blood draws for up to 10 years following STIC lesion diagnosis.
• Willing and able to provide informed consent in English

Exclusion criteria

Cohort A:

• Pregnant or breastfeeding at the time of enrollment.
• Prior removal of bilateral fallopian tubes and/or bilateral ovaries.
• Active diagnosis of cancer.
• Prior or active diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer at the time of consent.
• Patients with a history of cancer are eligible when > 2 years no evidence of disease.
• Inability to provide informed consent.
• Concurrent participation in another interventional trial that may confound study outcomes.

Cohort B:

• Pregnant or breastfeeding at the time of enrollment.
• Active diagnosis of cancer.
• Prior or active diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer at the time of consent (prior STIC lesion is NOT a contraindication to enrollment).
• Patients with a history of cancer are eligible when > 2 years no evidence of disease.
• Inability to provide informed consent.
• Concurrent participation in another interventional trial that may confound study outcomes.