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.

Background

ET represents a cornerstone in the treatment of early and late hormone receptors-positive (HR+) BC. However, adherence to ET is a major issue that can substantially impact survival outcomes. We explored whether PDDI with ET impact adherence.

Methods

We scanned the French version of the THIN™ database for women who had a reported diagnosis of BC and received ET (tamoxifen [tam] or aromatase inhibitor [AI]) between 1994 and 2021. Adherence was measured annually and defined by a medication possession ratio (MPR) ≥ 80% over 1-year prescription period. PDDI was classified using the Claude Bernard Drug Database into absent, minor (combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended) and contraindicated. We used repeated-measure regression models to estimate odds ratios (OR) for the correlation between MPR ≥ 80% and age, baseline comorbidities, PDDI, and MPR during the previous year. Among patients with multiple PDDI, the worse PDDI category by patient was retained and included in the multivariable model.

Results

Among the 10,863 eligible pts, polypharmacy ≥ 5 drugs was reported in 33.7% and 47.8% of the tam and AI cohorts. PDDI occurrence is summarized in the table. PDDI were mostly moderate in the tam (60.4-80.6%) and AI (94.7%-99.3%) cohorts; contraindicated combinations were below 1%. In the tam cohort, annual MPR ≥ 80% was 79.3% (n = 2,824) at year 1 and 89.5% (n = 426) at year 5. The association between MPR ≥ 80% and presence of PDDI was not statistically significant neither in the tam (OR 0.991, 95% CI 0.0.914-1.075) nor AI (OR 1.046, 95% CI 0.954-1.147) cohorts. Table: 225P

Prevalence of PDDI with ET at baseline and during follow up

Conclusions

Adherence to ET was not associated with PDDI in patients with HR+ BC treated with tam or AI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Bardet: Financial Interests, Personal, Other: Roche SAS. O. Bougacha, L. Gantzer, B. Lekens: Financial Interests, Full or part-time Employment: Cegedim R&D. I.V. Luis: Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: AstraZeneca. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/Servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, Orion, Sanofi; Financial Interests, Institutional, Advisory Board, Ad Board: Besins Healthcare; Financial Interests, Institutional, Funding: GE; 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. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Other, Founder: Pegacsy. S. Michiels: Financial Interests, Personal, Other, Statistical advice: IDDI, Amaris, Roche; Financial Interests, Personal, Other, DSMB member: Sensorion, Servier, Biophytis, Yuhan. B. Pistilli: Financial Interests, Institutional, Advisory Role: AstraZeneca, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Myriad, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Novartis, Puma; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, Pierre Fabre, MSD. All other authors have declared no conflicts of interest.