Trial of Combined Obstetric Carrier Screening and Hereditary Cancer Screening

Official title

Feasibility of Obstetric and Cancer Universal Screening

Overview

The investigators hypothesize that pregnancy and preconception care may be a feasible and effective time to offer inherited cancer risk screening. This study will assess interest in cancer genetic testing among patients receiving routine prenatal or preconception/fertility care. The goal is to evaluate the acceptability of BRCA1/2 testing when offered alongside standard prenatal genetic screening. The study will also explore whether universal screening in this population could support early cancer prevention and be cost-effective, especially among underserved populations.

Detailed description

The purpose of this study is to prospectively offer obstetric patients combined hereditary cancer screening (HCS) and obstetric carrier screening (OCS) to see if patients decide they want HCS in addition to their OCS. Preconception and pregnancy represent a unique window of opportunity for women to engage and interact with the healthcare system. With the proposed trial, the investigators aim to change the paradigm of obstetrical-related genetic testing to include potentially life-saving HCS.

Approximately 25% of the general population in the U.S. meets established criteria to recommend genetic counseling and testing for hereditary cancer syndromes, but less than 1% of individuals undergo genetic testing. Furthermore, racial, ethnic, and linguistic minorities experience even greater under-recognition of familial cancer syndromes.This results in a critical missed opportunity for preventing cancer-associated morbidity and mortality. Obstetric care is a potential window of opportunity for addressing this issue, as pregnancy offers a unique opportunity for individuals to interact with the healthcare system. Importantly, patients are already being introduced to the topics of genetic testing and counseling, as the American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women receive information regarding carrier screening. The uptake of OCS to evaluate hundreds of disorders is increasing rapidly, with a recent meta-analysis finding that 39% of patients undergo such testing. Currently, however, most cancer-associated mutations are not included in OCS assays. Screening reproductive-age women presents a unique opportunity to perform testing at a time when precancer screening, chemoprevention, and/or risk-reducing surgery is most beneficial.

Limited prior literature suggests that 50-75% of patients would accept combined HCS/OCS if offered. The investigators offered hereditary cancer risk assessment to 100 obstetrical patients in a diverse, Medicaid-predominant Weill Cornell Medicine clinic and found that 66% of patients were interested in cancer risk assessment during pregnancy. Furthermore, the investigators recently published a cost-effectiveness analysis suggesting that incorporation of BRCA1 genetic testing to all patients, regardless of family history at the time of OCS, is a cost-effective management strategy that can result in the prevention of breast and ovarian cancer cases and cancer deaths. Additionally, patient interviews suggest that more than 50% of patients mistakenly believed their OCS included cancer genes. This misconception poses a significant risk, as these patients assume that they had comprehensive testing and no hereditary cancer risk. Therefore, additional testing was believed to be unnecessary. Finally, prior theoretical patient surveys suggest high levels of interest in this combination testing among ethnically diverse populations. However, there has yet to be a prospective study offering patients the combined HCS/OCS, and all reported interests remain theoretical.

Interventions

• Genetic MyRisk Hereditary Cancer Test
  Subjects that are planning to proceed with OCS and enrolled in the trial will be contacted by the genetics clinician (by telephone or in person, based on subject preference) to review the option for HCS in addition to OCS. The WCM genetics clinician will review the potential risks and benefits, possible findings, and implications of findings for HCS. The genetics clinician will follow WCM standards (outlined by the WCM Genetics and Personalized Cancer Prevention Program https://wcinyp.org/GPCP)

Primary outcome measures

• Percentage of Participants Who Complete Both HCS and OCS [Time frame: Approximately within the end of recruitment expected at 2 years]

Secondary outcome measures (7)

• Percentage of Participants Completing Both HCS and OCS, Stratified by Demographic and Clinical Characteristics [Time frame: Approximately at the end of recruitment, expected at 2 years.]
• Percentage of High-Risk Participants Utilizing Guideline-Based Cancer Mitigation Strategies [Time frame: From completion of screening up to 18 months post-screening]
• Participant Experience with Combined HCS and OCS measured by the NCCN Distress Thermometer [Time frame: The questionnaire is received right after genetic counseling regarding HCS has been received.]
• Participant Experience with Combined HCS and OCS measured by Satisfaction with Genetic Counseling Scale [Time frame: The questionnaire is received right after genetic counseling regarding HCS has been received.]
• Participant Experience with Combined HCS and OCS measured by Satisfaction with Decision Scale [Time frame: The questionnaire is received right after genetic counseling regarding HCS has been received.]
• Participant Experience with Combined HCS and OCS - Qualitative Interview [Time frame: From completion of screening up to 18 months post-screening]
• Provider Experience with Combined HCS and OCS - Qualitative Interview [Time frame: From completion of screening up to 18 months post-screening]

Eligibility criteria

Inclusion criteria

• Age 18 years - 55 years
• Pregnant patients receiving obstetrical-related care or receiving preconception/fertility care at a WCM-affiliated enrollment site.
• Patients who have elected to undergo OCS with the WCM-affiliated obstetrics provider
• Patients with prior OCS but planned to repeat OCS are eligible
• Patients can speak and read in English or Spanish

Exclusion criteria

• Patients who have previously completed a multigene hereditary cancer syndrome panel
• Patients who have a hematologic cancer or hematologic pre-cancer
• Patients who have a history of an autologous bone marrow transplant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 5 centers

• Reproductive Medicine — Brooklyn
• NewYork-Presbyterian Weill Cornell Medicine — Brooklyn
• Reproductive Medicine — New York
• Weill Cornell Medicine — New York
• NewYork-Presbyterian Weill Cornell Medicine Queens — Queens

Publications

• Palinkas LA, Horwitz SM, Green CA, Wisdom JP, Duan N, Hoagwood K. Purposeful Sampling for Qualitative Data Collection and Analysis in Mixed Method Implementation Research. Adm Policy Ment Health. 2015 Sep;42(5):533-44. doi: 10.1007/s10488-013-0528-y. PMID 24193818
• Kaphingst KA, Bather JR, Daly BM, Chavez-Yenter D, Vega A, Kohlmann WK. Interest in Cancer Predisposition Testing and Carrier Screening Offered as Part of Routine Healthcare Among an Ethnically Diverse Sample of Young Women. Front Genet. 2022 Apr 14;13:866062. doi: 10.3389/fgene.2022.866062. eCollection 2022. PMID 35495140
• Dioun SM, Perez LR, Prabhu M, Brewer JT, Ahsan MD, Hou JY, Sharaf RN, Wright JD, Frey MK. Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention. Am J Obstet Gynecol. 2024 Sep;231(3):330.e1-330.e14. doi: 10.1016/j.ajog.2024.04.014. Epub 2024 Apr 14. PMID 38621481
• Grant BJ, Chandler I, Son M, Dioun S, Mcdougale A, Sharaf RN, Frey MK. Pregnancy: an underutilized window of opportunity for genetic cancer risk assessment. Am J Obstet Gynecol. 2025 Jan;232(1):e11-e13. doi: 10.1016/j.ajog.2024.09.100. Epub 2024 Sep 19. No abstract available. PMID 39306315
• Zhong L, Bather JR, Daly BM, Kohlmann WK, Goodman MS, Rothwell E, Kaphingst KA. Investigation of interest in and timing preference for cancer predisposition testing and expanded carrier screening among women of reproductive age. PEC Innov. 2023 Jan 24;2:100128. doi: 10.1016/j.pecinn.2023.100128. eCollection 2023 Dec. PMID 37214524
• Edwards JG, Feldman G, Goldberg J, Gregg AR, Norton ME, Rose NC, Schneider A, Stoll K, Wapner R, Watson MS. Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Mater PMID 25730230
• Goldberg JD, Pierson S, Johansen Taber K. Expanded carrier screening: What conditions should we screen for? Prenat Diagn. 2023 Apr;43(4):496-505. doi: 10.1002/pd.6306. Epub 2023 Jan 18. PMID 36624552
• Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol. 2017 Mar;129(3):e41-e55. doi: 10.1097/AOG.0000000000001952. PMID 28225426

Identifiers

NCT: NCT07052266 · 25-02028559

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗