D. G. Evans (Manchester, United Kingdom)
The University of ManchesterAuthor Of 3 Presentations
Feasibility and acceptability of risk based screening including reduced screening in low risk women (ID 444)
135P - Real time genotyping-based breast cancer risk assessment in MyPeBS, an International randomized trial in the general population comparing risk-stratified to standard breast cancer screening (BCS) (ID 148)
- Suzette Delaloge (Villejuif, France)
- Paolo Giorgi Rossi (Guastalla, Italy)
- Corinne Balleyguier (Villejuif, Cedex, France)
- Michal Guindy (Tel Aviv, Israel)
- Fiona J. Gilbert (Cambridge, United Kingdom)
- Jean-Benoit Burrion (Brussels, Belgium)
- Marta Roman (Barcelona, Spain)
- Sandrine De Montgolfier (Aubervilliers, France)
- Livia Giordano (Torino, Italy)
- Damien Drubay (Villejuif, Cedex, France)
- D. G. Evans (Manchester, United Kingdom)
- Deborah Keatley (London, United Kingdom)
- Emilien Gauthier (Villejuif, Cedex, France)
- Aloys Du Bois d'Aische (Mons, Belgium)
- Camille Baron (Paris, France)
- Anne Boland (Evry, France)
- Hélène Blanché (Paris, France)
- Daniel Couch (Paris, France)
- Jean-François Deleuze (Evry, France)
- Stefan Michiels (Villejuif, Cedex, France)
Abstract
Background
Risk-stratified BCS, integrating personal, familial variables and a polygenic risk score (PRS) is a promising strategy that may improve current BCS outcomes. Real-time risk assessment and field implementation are some of the main challenges for such an approach.
Methods
MyPeBS is an ongoing EU-funded international randomized trial running in 6 countries. Eligible women (wn) aged 40-70 are randomized 1:1 between continuing standard organized BCS as recommended in their participating country/region and switching to risk-stratified BCS, in which BCS schedule and modalities are adapted to the individual predicted 5-year risk of invasive BC (IBC). Primary endpoint is 4-year incidence of stage 2 and higher BC. Secondary endpoints include PROs. 5-year IBC risk is estimated using the Mammorisk® BCSC-derived or the Tyrer Cuzick risk score and the centrally-determined PRS313 obtained from a saliva sample and calibrated for national BC incidence and age. We aim to describe 1) the feasibility of real-time assessment of BC risk and 2) the characteristics and risk profiles of the participants.
Results
As of Sept. 7, 2021, 16,550 wn had been randomized. 29% were aged <50 (median age 54 (range 40-70), 13% had a previous benign breast biopsy, 40% a mammographic breast density C or D, 19% a 1st degree family history of breast or ovarian cancer; 72% had tertiary education. 36% were estimated at low risk (<1% risk of IBC at 5 years), 29% at average risk, and 35% at high (34%) or very high risk (1%) (>1.67% and >6% risk, respectively). Only 2.5% of DNA extractions were not usable for genotyping, due to DNA concentration or quality; and 98.8% of the eligible DNA samples were successfully genotyped. Median turnover time from saliva sampling to risk result available was 11 weeks despite the COVID pandemic (currently 7 weeks).
Conclusions
Real-time BC risk assessment based on a large set of polymorphisms, family, screening and hormonal history, and breast density is feasible within organized screening programmes. Participants are so far representative of different categories with some over-representation of highly educated participants.
Clinical trial identification
NCT03672331.
Legal entity responsible for the study
Unicancer.
Funding
European Commission and French National Cancer Institute.
Disclosure
S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. D. Keatley: Financial Interests, Personal, Advisory Board: Public Advisory Board of Heealth Data UK. E. Gauthier: Financial Interests, Personal, Stocks/Shares: Predilife; Financial Interests, Personal, Full or part-time Employment: Predilife. S. Michiels: Financial Interests, Personal, Advisory Role: IDDI; Financial Interests, Personal, Advisory Role: Amaris; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sensorion; Financial Interests, Personal, Advisory Role: Biophytis; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Yuhan. All other authors have declared no conflicts of interest.
156TiP - BRCA-DIRECT: A randomised UK study evaluating a digital pathway for germline genetic testing and non-inferiority of digitally-delivered information in women with breast cancer. (ID 169)
- Bethany Torr (Sutton, United Kingdom)
- Subin Choi (London, United Kingdom)
- Chris Jones (Brighton, United Kingdom)
- Sophie Allen (London, United Kingdom)
- Grace Kavanaugh (London, United Kingdom)
- Monica Hamill (London, United Kingdom)
- Kathryn Monson (Brighton, United Kingdom)
- Suzanne Machmahon (London, United Kingdom)
- Mikel Valgon Petrizan (London, United Kingdom)
- Lesley J. Fallowfield (Brighton, United Kingdom)
- Valerie Jenkins (Brighton, United Kingdom)
- Angela George (London, United Kingdom)
- D. G. Evans (Manchester, United Kingdom)
- Ashu Gandhi (Manchester, United Kingdom)
- Zoe Kemp (London, United Kingdom)
- Michael Hubank (London, United Kingdom)
- Clare Turnbull (London, United Kingdom)
Abstract
Background
Germline genetic testing affords multiple opportunities for women with breast cancer relating to (i) treatment of a current breast cancer, (ii) management of risk of future cancers, and (iii) identification of at-risk family members. In the UK, testing remains restricted to individuals at highest a-priori risk of carrying a pathogenic variant (<20% of women diagnosed with a breast cancer). The main barrier to expanding testing is a shortage of clinical resource due to current requirements to complete complex eligibility assessments, 1:1 pre-test genetic counselling, and pathway management. Routes enabling expansion of genetic testing in routine cancer care are currently a key area of focus within the NHS. Much of the information and process for germline genetic testing of cancer patients are generic and predictable. We hypothesise that if a specialist genetic hotline were available to support the minority with individualised issues, testing for the majority could be managed end-to-end more rapidly and efficiently via a clinically-integrated digital system providing consistent, accurate information.This would reduce the clinical resource and the overall cost of the testing pathway.
Trial design
BRCA-DIRECT aims to test this hypothesis by evaluating a digital pathway for germline testing of BRCA1, BRCA2 and PALB2 in 1000 unselected women with breast cancer recruited from two UK oncology centres (Royal Marsden NHS Foundation Trust and Manchester University NHS Foundation Trust). Patients provide a saliva sample at point of consent and the remainder of tasks are completed digitally, including family history questionnaire, genetic test consent and receipt of negative results or appointment bookings for return of positive results. Patients are randomised 1:1 to receive pre-test information via the digital “BRCA-DIRECT” platform or from a Genetic Counsellor via telephone appointment The primary outcome is to assess non-inferiority in uptake of genetic testing for digital vs telephone delivery of pre-test information. Other outcome measures include: participant anxiety, knowledge, hotline use, and participant and clinician satisfaction.
Clinical trial identification
Protocol/serial number: CPMS 47406, IRAS 278052 https://doi.org/10.1186/ISRCTN87845055.
Legal entity responsible for the study
Institute of Cancer Research, United Kingdom.
Funding
Cancer Research UK.
Disclosure
All authors have declared no conflicts of interest.