Implementing Polygenic Risk Scores for Breast Cancer Prevention: a Feasibility Study

NCT06922708 | Recruiting

• 2 other identifiers: 7310No. D.D. 931
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm interventional feasibility study will evaluate whether integrating polygenic risk scores (PRS) into the CanRisk model can improve breast cancer risk prediction and personalized prevention in women at risk of breast cancer. The study will assess the organizational feasibility, patient acceptance, emotional impact and satisfaction of an integrated pathway combining PRS testing with standard genetic counseling and other risk factors at Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Conditions

Breast Cancer

Keywords

breast cancer; risk stratification; polygenic risk score; CanRisk model; feasibility study; personalized prevention

Outcome Measures

Primary Outcomes (1)

• Feasibility of implementing an integrated clinical pathway including PRS

  The primary outcome is the feasibility of integrating polygenic risk score (PRS) testing into the CanRisk breast cancer risk model within a structured clinical pathway. Feasibility will be assessed using the Care Process Self-Evaluation Tool (CPSET), that includes 27 items across 5 domains: patient-centeredness, coordination of care, communication, cooperation, and monitoring/follow-up. The questionnaire will be administered at the end of the study to both enrolled women and involved healthcare professionals.

  At 12 months from enrollment

Secondary Outcomes (6)

• Uptake of CanRisk+PRS integrated pathway

  At the time of enrollment, when eligible participants are offered PRS testing

• Proportion of women requesting their individual CanRisk+PRS result

  At month 12.

• Percentage of women reclassified into different risk categories after PRS integration

  At month 12

• Proportion of women with modified prevention pathways after PRS-informed reclassification

  At month 12.

• Perception of risk and psychological impact

  At month 12

Study Arms (1)

Integrated PRS-enhanced breast cancer risk assessment

EXPERIMENTAL

Women attending a Medical Genetics Clinic for breast cancer risk assessment, all undergoing CanRisk evaluation with and without PRS, without allocation to different interventions.

Genetic: Clinical pathway for breast cancer prevention based on PRS-integrated CanRisk assessment

Interventions

Clinical pathway for breast cancer prevention based on PRS-integrated CanRisk assessment GENETIC

Standard genetic counseling followed by a blood draw (0.5 mL) for DNA extraction. The sample is processed using a high-throughput SNP genotyping platform, and the PRS, based on 313 SNPs, is calculated and integrated into the CanRisk model for refined breast cancer risk stratification. In conjunction with result disclosure, participants complete structured questionnaires to assess psychological impact and risk comprehension (questionnaire by Woof et al.). At the end of the study, both participants and healthcare professionals complete feasibility questionnaires to evaluate the implementation of the PRS-integrated clinical pathway (Care Process Self-Evaluation Tool, CPSET; Vanhaecht et al.).

Integrated PRS-enhanced breast cancer risk assessment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• Voluntary consent to participate
• Estimated risk of carrying an inherited pathogenic variant (in BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1) \> 5%, (calculated on www.canrisk.org)
• Healthy women with:
• Known family history of breast cancer, or
• Known familiarity with carriers of pathogenic variants for genes included in the CanRisk model (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1), or
• Known carriers of pathogenic variants for genes included in the CanRisk model (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1)
• Affected women with:
• Diagnosis of unilateral breast cancer
• Personal history of ovarian cancer

You may not qualify if:

• Diagnosis or history of bilateral breast cancer
• Diagnosis of ductal carcinoma in situ
• Previous bilateral mastectomy
• Life expectancy \< 12 months due to other medical conditions
• Participation in interventional clinical trials for breast cancer prevention in the last 12 months
• Carriers or relatives of carriers of pathogenic variants in genes not included in the CanRisk model (genes other than BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1)
• Inability to provide informed consent

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead

Study Sites (1)

Policlinico Universitario Fondazione Agostino Gemelli

Roma, Italy

RECRUITING

Related Publications (14)

• Vanhaecht K, De Witte K, Depreitere R, Van Zelm R, De Bleser L, Proost K, Sermeus W. Development and validation of a care process self-evaluation tool. Health Serv Manage Res. 2007 Aug;20(3):189-202. doi: 10.1258/095148407781395964.

  PMID: 17683658 BACKGROUND

• Du Z, Gao G, Adedokun B, Ahearn T, Lunetta KL, Zirpoli G, Troester MA, Ruiz-Narvaez EA, Haddad SA, PalChoudhury P, Figueroa J, John EM, Bernstein L, Zheng W, Hu JJ, Ziegler RG, Nyante S, Bandera EV, Ingles SA, Mancuso N, Press MF, Deming SL, Rodriguez-Gil JL, Yao S, Ogundiran TO, Ojengbe O, Bolla MK, Dennis J, Dunning AM, Easton DF, Michailidou K, Pharoah PDP, Sandler DP, Taylor JA, Wang Q, Weinberg CR, Kitahara CM, Blot W, Nathanson KL, Hennis A, Nemesure B, Ambs S, Sucheston-Campbell LE, Bensen JT, Chanock SJ, Olshan AF, Ambrosone CB, Olopade OI, Yarney J, Awuah B, Wiafe-Addai B, Conti DV; GBHS Study Team; Palmer JR, Garcia-Closas M, Huo D, Haiman CA. Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry. J Natl Cancer Inst. 2021 Sep 4;113(9):1168-1176. doi: 10.1093/jnci/djab050.

  PMID: 33769540 BACKGROUND

• Lakeman IMM, Rodriguez-Girondo M, Lee A, Ruiter R, Stricker BH, Wijnant SRA, Kavousi M, Antoniou AC, Schmidt MK, Uitterlinden AG, van Rooij J, Devilee P. Validation of the BOADICEA model and a 313-variant polygenic risk score for breast cancer risk prediction in a Dutch prospective cohort. Genet Med. 2020 Nov;22(11):1803-1811. doi: 10.1038/s41436-020-0884-4. Epub 2020 Jul 6.

  PMID: 32624571 BACKGROUND

• Archer S, Donoso FS, Carver T, Yue A, Cunningham AP, Ficorella L, Tischkowitz M, Easton DF, Antoniou AC, Emery J, Usher-Smith J, Walter FM. Exploring the barriers to and facilitators of implementing CanRisk in primary care: a qualitative thematic framework analysis. Br J Gen Pract. 2023 Jul 27;73(733):e586-e596. doi: 10.3399/BJGP.2022.0643. Print 2023 Aug.

  PMID: 37308304 BACKGROUND

• Vassy JL, Brunette CA, Lebo MS, MacIsaac K, Yi T, Danowski ME, Alexander NVJ, Cardellino MP, Christensen KD, Gala M, Green RC, Harris E, Jones NE, Kerman BJ, Kraft P, Kulkarni P, Lewis ACF, Lubitz SA, Natarajan P, Antwi AA. The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care. Am J Hum Genet. 2023 Nov 2;110(11):1841-1852. doi: 10.1016/j.ajhg.2023.10.001.

  PMID: 37922883 BACKGROUND

• Tsoulaki O, Tischkowitz M, Antoniou AC, Musgrave H, Rea G, Gandhi A, Cox K, Irvine T, Holcombe S, Eccles D, Turnbull C, Cutress R; Meeting Attendees; Archer S, Hanson H. Joint ABS-UKCGG-CanGene-CanVar consensus regarding the use of CanRisk in clinical practice. Br J Cancer. 2024 Jun;130(12):2027-2036. doi: 10.1038/s41416-024-02733-4. Epub 2024 Jun 4.

  PMID: 38834743 BACKGROUND

• Mbuya-Bienge C, Pashayan N, Kazemali CD, Lapointe J, Simard J, Nabi H. A Systematic Review and Critical Assessment of Breast Cancer Risk Prediction Tools Incorporating a Polygenic Risk Score for the General Population. Cancers (Basel). 2023 Nov 12;15(22):5380. doi: 10.3390/cancers15225380.

  PMID: 38001640 BACKGROUND

• Hovhannisyan M, Zemankova P, Nehasil P, Matejkova K, Borecka M, Cerna M, Dolezalova T, Dvorakova L, Foretova L, Horackova K, Jelinkova S, Just P, Kalousova M, Kral J, Machackova E, Nemcova B, Safarikova M, Springer D, Stastna B, Tavandzis S, Vocka M, Zima T, Soukupova J, Kleiblova P, Ernst C, Kleibl Z, Janatova M. Population-specific validation and comparison of the performance of 77- and 313-variant polygenic risk scores for breast cancer risk prediction. Cancer. 2024 Sep 1;130(17):2978-2987. doi: 10.1002/cncr.35337. Epub 2024 May 8.

  PMID: 38718029 BACKGROUND

• Yang X, Eriksson M, Czene K, Lee A, Leslie G, Lush M, Wang J, Dennis J, Dorling L, Carvalho S, Mavaddat N, Simard J, Schmidt MK, Easton DF, Hall P, Antoniou AC. Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study. J Med Genet. 2022 Dec;59(12):1196-1205. doi: 10.1136/jmg-2022-108806. Epub 2022 Sep 26.

  PMID: 36162852 BACKGROUND

• Lee A, Mavaddat N, Wilcox AN, Cunningham AP, Carver T, Hartley S, Babb de Villiers C, Izquierdo A, Simard J, Schmidt MK, Walter FM, Chatterjee N, Garcia-Closas M, Tischkowitz M, Pharoah P, Easton DF, Antoniou AC. BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet Med. 2019 Aug;21(8):1708-1718. doi: 10.1038/s41436-018-0406-9. Epub 2019 Jan 15.

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Related Links

• This website provides the calculator of the CanRisk score

MeSH Terms

Conditions

Breast Neoplasms; Genetic Risk Score

Interventions

Critical Pathways

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Patient Care Planning; Comprehensive Health Care; Patient Care Management; Health Services Administration

Study Officials

• Stefania Boccia, Phd

  Life Sciences and Public Health Department, Università Cattolica del Sacro Cuore, Rome, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Farina, MD

CONTACT

0039 + 0630156808; sarafarins96@gmail.com

Francesco A Causio, MD

CONTACT

francescoandrea.causio@unicatt.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Hygiene and Preventive Medicine

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: April 10, 2025
• Study Start: June 6, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: August 3, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication of the study results and will remain available indefinitely.
• Access Criteria: Researchers wishing to access the de-identified individual participant data (IPD) and supporting documentation must submit a formal request that includes a research proposal outlining the planned analyses and justification for data use. All requests will be reviewed by the study's Data Access Committee to ensure that the proposed research meets ethical and scientific criteria. A data sharing agreement, detailing the conditions for data use and protecting participant confidentiality, must be signed before access is granted. Detailed submission instructions and contact information will be provided on the secure repository platform.

Locations

IT (1)