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

NCT06922708 | Not Yet Recruiting

• 2 other identifiers: 7310No. D.D. 931
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this single-arm interventional study is to learn whether integrating a polygenic risk score (PRS) into the CanRisk model can help improve breast cancer risk prediction and prevention in adult women with or without a family history of breast cancer and in women diagnosed with unilateral breast cancer. The main questions it aims to answer are:

• Provide a blood sample for PRS testing and for pathogenetic variants for breast cancer risk (if they have not already had genetic testing).
• Complete a questionnaire on their experience and acceptance of PRS. Because this is a single-arm study, there is no separate comparison group. The study team will use the results to see how well PRS can be integrated into clinical care and whether it offers any improvements in prevention strategies for breast cancer.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of women accessing the pathway

  At the time of participant enrollment in the clinical pathway for risk assessment.

• Acceptance rate

  Percentage of women accepting PRS testing among those offered

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

Secondary Outcomes (4)

• Qualitative assessment of PRS fesibility among healthcare professionals, using the CPSET questionnaire

  At the end of the 12-month study period.

• Qualitative assessment of PRS feasibility among patients, using CPSET questionnaire

  Immediately after receiving their genetic counseling (on average 2-4 weeks after enrollment).

• Risk reclassification rate

  Through study completion, up to 12 months.

• Distribution of participants across low, moderate, and high breast cancer risk categories before and after integration of PRS

  Through study completion, up to 12 months (the final distribution is calculated once all participants have received their PRS results).

Study Arms (1)

Integrated PRS-enhanced breast cancer risk assessment arm

EXPERIMENTAL

Participants in this experimental (signle) arm will undergo an integrated breast cancer risk assessment combining the CanRisk model with polygenic risk score (PRS) testing. The intervention includes genetic counseling, blood collection for PRS analysis, and a comprehensive risk evaluation. Additionally, participants will complete a questionnaire to gather their feedback on the integrated PRS clinical pathway.

Diagnostic Test: Integrated PRS-Enhanced Breast Cancer Risk Assessment (CanRisk model)

Interventions

Integrated PRS-Enhanced Breast Cancer Risk Assessment (CanRisk model) DIAGNOSTIC_TEST

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.

Integrated PRS-enhanced breast cancer risk assessment arm

Eligibility Criteria

• Age: 18 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
• CanRisk score (without PRS) \> 5% (calculated on www.canrisk.org)
• Healthy women with:
• Known family history of breast cancer, or
• Known family history of genetic conditions associated with increased breast cancer risk, or
• Known carriers of pathogenic variants (BRCA1, BRCA2, PALB2, CHEK2, ATM, PTEN, TP53, CDH1)
• Affected women with:
• Diagnosis of unilateral breast cancer
• Personal history of ovarian cancer

You may not qualify if:

• CanRisk score (without PRS) \< 5% (calculated on www.canrisk.org)
• Diagnosis or history of bilateral breast cancer
• 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
• Inability to provide informed consent

Sponsors & Collaborators

• Boccia Stefania: lead
• Catholic University of the Sacred Heart: collaborator

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.

  PMID: 30643217 BACKGROUND

• Qaseem A, Lin JS, Mustafa RA, Horwitch CA, Wilt TJ; Clinical Guidelines Committee of the American College of Physicians; Forciea MA, Fitterman N, Iorio A, Kansagara D, Maroto M, McLean RM, Tufte JE, Vijan S. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians. Ann Intern Med. 2019 Apr 16;170(8):547-560. doi: 10.7326/M18-2147. Epub 2019 Apr 9.

  PMID: 30959525 BACKGROUND

• Canelo-Aybar C, Posso M, Montero N, Sola I, Saz-Parkinson Z, Duffy SW, Follmann M, Grawingholt A, Giorgi Rossi P, Alonso-Coello P. Benefits and harms of annual, biennial, or triennial breast cancer mammography screening for women at average risk of breast cancer: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC). Br J Cancer. 2022 Mar;126(4):673-688. doi: 10.1038/s41416-021-01521-8. Epub 2021 Nov 26.

  PMID: 34837076 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Visvanathan K. USPSTF recommends biennial mammography for breast cancer screening in women aged 40 to 74 y. Ann Intern Med. 2024 Oct;177(10):JC110. doi: 10.7326/ANNALS-24-02229-JC. Epub 2024 Oct 1.

  PMID: 39348703 BACKGROUND

Related Links

• This website provides the calculator of the CanRisk score

MeSH Terms

Conditions

Breast Neoplasms; Genetic Risk Score

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

Study Officials

• Stefania Boccia, Phd

  Dipartimento di Scienze della Vita e Sanità Pubblica, 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: SPONSOR 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 9, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: June 3, 2025

Record last verified: 2025-05

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.