BRIGHT Seminar in Uppsala: unveiling first results of precision breast cancer prevention

On Monday, April 22nd, a seminar titled “Breast Cancer Precision Prevention – Presenting Results from Sweden, Estonia and Portugal” was held at the Uppsala University Hospital. The seminar showcased preliminary results and explored opportunities for the implementation of breast cancer precision prevention in healthcare. 

EIT Health-funded BRIGHT project investigates stratified breast cancer screening based on genetic risk estimated with polygenic risk scores (PRS). The purpose of the study is to improve opportunities for early detection of breast cancer based on genetic risk, as opposed to today’s standardised mammography screening based solely on age. Across all countries participating in the BRIGHT project, women between the ages 30-49 are assessed for their genetic predisposition to breast cancer and personalised risk-based screening recommendations are provided. The project uses innovative clinical-grade polygenic risk score test AnteBC, which is developed by health technology company Antegenes

The BRIGHT study (Be RIGHT with Breast Cancer Risk Management) was initiated in 2022 in Sweden, Estonia and Portugal. In Sweden and Estonia the clinical implementation study is finished and 1600 women were recruited in total. Volunteer recruitment in Portugal ends in May 2024. The logistical and ethical considerations and information flow are also assessed in the clinical pilot. In addition, cost-utility of the precision breast cancer prevention is evaluated.

Initial results from Sweden

In Sweden, recruitment utilized media channels, websites and an email address for participant communication. Recruitment was conducted through a form in the digital registration system, which included information about the study, survey data and contact information. By the end of March, the planned number of study participants had been reached, as approximately 800 individuals expressed interest in participating. Each participant received an AnteBC test kit, including instructions and a return envelope, which they could easily do as a home based test. 

Upon analysis, participants were categorised into three groups based on the PRS test results: those with low to average risk (less than or up to the population average risk RR = <1.5), slightly elevated risk (RR = 1.5 – 2.7) and elevated risk (RR = ≥ 2.7). It revealed that 16% of participants had a slightly elevated risk, while 83% exhibited a lower or average risk and 1% had an elevated risk. Prof. Inna Feldman, health economist and project manager for the study in Uppsala, explained that women identified with a low to average risk were provided with a report and a letter containing recommendations. Those with slightly elevated or elevated risk levels received a report, a recommendation letter, and an offer for a consultation. 

At the seminar, Filipa Sampaio, a health economist at Uppsala University, gave a presentation titled “Cost-effectiveness analysis of a polygenic risk-tailored breast cancer screening – the BRIGHT project experience.” Inna Feldman stated about the presentation that they have conducted a cost-effectiveness analysis, examining various scenarios including PRS-based screening, focusing on personalised services for women in different risk categories. Alongside more frequent mammography screening for women at elevated risk of breast cancer, they also assessed a scenario where women at low risk would commence screening at a later stage than currently recommended.

Feedback was collected from all participants, resulting in a response rate of 60%. “92% of respondents indicated that they were glad they had the opportunity to participate in the BRIGHT study and 87% reported feeling calm regarding the results,” highlighted Prof. Inna Feldman. Additionally, she noted that 75% of respondents found the explanations provided about the genetic risk and the clinical recommendations to be understandable.

Strong interest from women in Portugal and Estonia

The Portuguese branch of the BRIGHT study has recruited 653 volunteers so far, during the study period one case of invasive breast cancer was diagnosed. There has been a lot of interest in study participation and genetic testing.The study has surprisingly revealed that many women have already had a mammograms before screening. However, regular self-examination wasn’t common among participants, especially those from high-risk families.

The study highlighted a need for increased awareness and understanding of genetic testing, as well as clear communication of results by healthcare professionals. “Moving forward, our focus is on integrating polygenic risk scores into clinical practice and disseminating study findings to relevant stakeholders,” said Prof. Luis Costa who is the project lead for the study in Portugal, emphasising the potential implications for national screening programs and cancer management protocols.

The Estonian branch of the clinical trial has concluded, and Estonian results will soon be published. Recruitment for the study was conducted through four different channels: Antegenes’ online portal offering home-based testing, selected pharmacies, Breast Clinic of Tartu University Hospital, and family physician services. The preliminary findings indicate that out of the 800 participants,15.9% had a recommendation to initiate their mammography screening already this year. “This means that the polygenic risk score testing had an immediate effect on their follow-up,” said the BRIGHT project activity leader Prof. Neeme Tõnisson from the University of Tartu. Within the Estonian arm of the project, 127 women underwent mammograms, with 16 benign changes identified and 8 women requiring further investigations.

Patient organisations advocating for breast cancer precision screening

At the seminar, there was also a discussion involving participation from patient organizations, as well as the Uppsala Breast Cancer Association and Region Uppsala. The participants in the discussion highlighted the importance of population-wide precision breast cancer screening services, the significance of educating women about PRS to improve health literacy, and emphasized the need to present the results to politicians and decision-makers.

Kim Höglund from the Uppsala Breast Cancer Association emphasized the importance of young women having access to PRS testing, to facilitate early diagnosis. “Early diagnosis is crucial. It’s very important that everyone knows about this opportunity and extensive information campaigns should be conducted for that purpose.” Additionally, they underscored the importance of developing explanations of PRS test results tailored to different levels of health literacy. Patient representatives expressed strong support for the broad implementation and equal access to PRS testing. The seminar was also attended by representatives and members from the Karolinska Institute, the Swedish Regional Cancer Center, EIT Health, Uppsala University, the University of Tartu and the Estonian Cancer Center, in addition to the consortium members.

A more comprehensive analysis of the study results will be published in collaboration with the study’s international partners in a peer-reviewed scientific journal article. The consortium convened in Sweden to discuss immediate steps necessary for implementing precision prevention initiatives in project countries and to outline plans for ongoing research collaboration. On October 10-11, a BRIGHT open seminar will take place in Portugal, where the initial results of the pilot study and cost-effectiveness analysis in Portugal will be presented at North Lisbon University Hospital.

BRIGHT project partners are Region Uppsala, North Lisbon University Hospital Centre, University of Tartu, Tartu University Hospital, Antegenes, Estonian Health Insurance Fund, IESE Business School and GE HealthCare. 

BRIGHT Breast Cancer Precision Prevention – Presenting Results from Sweden, Estonia and Portugal

EIT Health-funded BRIGHT project investigates stratified breast cancer screening based on genetic risk estimated with polygenic risk scores. This involves assessing women for their genetic predisposition to breast cancer from the age of 35 or 40 and provide personalized risk-based screening recommendations. The project includes clinical studies in Estonia, Sweden and Portugal. Each country has recruited 800 women in the clinical implementation study. 

The goal of the international BRIGHT project is to implement screening based on genetic risk assessment for breast cancer, involving research and innovation partners, healthcare providers, health insurance providers and patient organizations. 

BRIGHT project partners are Region Uppsala, North Lisbon University Hospital Centre, University of Tartu, Tartu University Hospital, Antegenes, Estonian Health Insurance Fund, IESE Business School and GE Healthcare. 

The seminar presents preliminary results and discusses the opportunities related to implementation of breast cancer precision prevention in healthcare. You can also participate in the event through Zoom by registering yourself in the registration form, and the link will be sent to your email before the event.

Date: Monday, April 22, 2024
Time: 14.00-16.00
Venue: Psykiatrin hus, Nordlandersalen
Akademiska Sjukhuset (Uppsala University Hospital)

Please inform us of your participation in the event by filling out the registration form: https://forms.gle/1c2EhqWR4gYkBXt18

Event Schedule:

14.00-14.05: Welcome and Introductions
Presenter: Ass. Prof. Inna Feldman, Region Uppsala

14.05-14.15: BRIGHT Project
Presenter: Prof. Neeme Tõnisson, University of Tartu

14.15-14.40: Clinical Study in Uppsala
Presenters: Ass. Prof. Inna Feldman, Region Uppsala
Ass. Prof. Andreas Karakatsanis, Uppsala University Hospital

14.40-14.55: BRIGHT Results from Other Countries – Estonia and Norway
Presenter: Dr. Krista Kruuv-Käo, Antegenes Estonia

14.55-15.10: BRIGHT Results from Other Countries – Portugal
Presenter: Prof. Luis Costa, Hospital de Santa Maria

15.10-15.35: Preliminary Cost-Effectiveness Results
Presenter: Ass. Prof. Filipa Sampaio, Region Uppsala

15.35-16.00: Panel Discussion
Moderator: Dr. Robert Kristiansson, Region Uppsala

Scientific Publication published in the journal “Breast Cancer: Basic and Clinical Research”

Our recently published peer-reviewed article, “Implementation of Risk-Stratified Breast Cancer Prevention With a Polygenic Risk Score Test in Clinical Practice,” in the journal “Breast Cancer: Basic and Clinical Research,” is one of the first scientific papers describing the introduction of a polygenic risk score into routine clinical practice. In the article, we detail the development and validation of a breast cancer polygenic risk score genetic test, the creation of its clinical usage model and test report, as well as initial results from its application in Estonian healthcare for breast cancer prevention based on individual genetic risks.

Implementation of Risk-Stratified Breast Cancer Prevention With a Polygenic Risk Score Test in Clinical Practice

Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have identified numerous genetic variants (single-nucleotide polymorphisms [SNPs]) associated with BC. The effects of SNPs are combined into a polygenic risk score (PRS) as a risk prediction tool. We aimed to develop a clinical-grade PRS test suitable for BC risk-stratified screening with clinical recommendations and implementation in clinical practice.

In the first phase of our study, we gathered previously published PRS models for predicting BC risk from the literature and validated them using the Estonian Biobank and UK Biobank data sets. We selected the best performing model based on prevalent data and independently validated it in both incident data sets. We then conducted absolute risk simulations, developed risk-based recommendations, and implemented the PRS test in clinical practice.

In the second phase, we carried out a retrospective analysis of the PRS test’s performance results in clinical practice. The best performing PRS included 2803 SNPs. The C-index of the Cox regression model associating BC status with PRS was 0.656 (SE = 0.05) with a hazard ratio of 1.66. The PRS can stratify individuals with more than a 3-fold risk increase. A total of 2637 BC PRS tests have been performed for women between the ages 30 and 83. Results in clinical use overlap well with expected PRS performance with 5.7% of women with more than 2-fold and 1.4% with more than 3-fold higher risk than the population average.

The PRS test separates different BC risk levels and is feasible to implement in clinical practice.

Read more here: https://journals.sagepub.com/doi/10.1177/11782234231205700

BRIGHT rinnavähi täppisennetuse projekti teavitusüritus – Eesti haru tulemused ja käsitlused

Hea Kolleeg! 

Olete väga oodatud BRIGHT projekti teavitusüritusele – kliinilise uuringu tulemused Eestis ja patsiendikäsitlus, mis toimub kolmapäeval, 8. novembril kl 15.0017.00 Tartus, Biomeedikumis, Alexander Schmidti keskuses (Ravila 19). Üritusel on võimalik osaleda ka virtuaalselt, registreerides ennast veebi teel osalejaks. BRIGHT Eesti teavitusüritusel tutvustatakse Eesti haru käsitlusi, tulemusi ning rinnavähi täppisennetuse rakendamist rahvusvahelisel tasandil. BRIGHT projekti Eesti partnerid on Tartu Ülikool, Tartu Ülikooli Kliinikum, meditsiinilabor Antegenes ja Tervisekassa. 

BRIGHT rahvusvahelise rakendusuuringu eesmärgiks on rinnavähi geneetilisel riskihinnangul põhineva sõeluuringu käivitamine, kaasates selleks teadus- ja innovatsioonipartnerid, tervishoiuteenuste osutajad, ravikindlustuse pakkujad ja patsiendiorganisatsioonid. 

Rinnavähi täppisennetus on kaasaegses käsitluses digilahendus, mis kombineerib tervisesüsteemis tarkvaralised veebilahendused, logistilised lahendused, tervishoiuasutuste koostöö, geenitestid ja neile järgnevad tervishoiuteenused ühtseks lahenduseks rinnavähi ennetusteenusena rinnavähist tingitud suremuse vähendamiseks. 

Teavitusüritusel osalemisest palume Teil teada anda hiljemalt 3. novembriks täites registreerumise vormi: https://forms.gle/Ck1gxdMMgM191aDM6.  

Ürituse ajakava:  

14.30–15.00 kogunemine, tervituskohv

15.00–16.30 ettekanded 

  • meditsiinigeneetika professor Neeme Tõnisson. Avasõnad ning BRIGHT projekti taust ja tutvustus, käsitluse üldine loogika (10 min)
  • onkoloog Peeter Padrik „BRIGHT projekti Eesti haru geneetiliste riskide analüüside tulemused“ (10 min)
  • pereõde Lota Kiiroja “Perearstikeskuse kogemus rinnavähi täppisennetuse uuringus”  (10 min)
  • meditsiiniõde Anette Paas „BRIGHT projekti Eesti haru patsientide tagasiside tulemused“ (10 min)
  • analüütik Katrin Lutsar „BRIGHT projekti PRS käsitluse kulutõhususanalüüsi tulemused“ (10 min)
  • dr Krista Kruuv-Käo „Rinnavähi täppisennetuse rakendamine Norras, AnteNOR projekti seis ja tulemused“ (10 min)
  • onkoloog professor Luis Costa „Breast cancer early detection program in Portugal“ (15 min)
  • professor Neeme Tõnisson ja dr Peeter Padrik „Geneetilistel riskidel põhinev rinnavähi täppisennetus. Vaade tagasi, vaade praegusele ja vaade tulevikku“ (15 min)


16.30–17.00 paneeldiskussioon „Kuidas jõuda Eestis parima personaliseeritud rinnavähi täppisennetuseni?“, modereerib professor Neeme Tõnisson

17.00–17.30 lõppsõna ja suupistelaud 

Osalema on kutsutud:  

Patsiendiorganisatsioonid, valdkonna erialaorganisatsioonid ja arstid, rinnavähi ennetustegevusega tegelevad raviasutused, Riigikogu sotsiaalkomisjoni, Sotsiaalministeeriumi, Tervisekassa, Tervise Arengu Instituudi esindajad, tervishoiuvaldkonna meedia esindajad, BRIGHT projekti partnerid, avalikkus. 

Loodame Teiega kohtuda BRIGHT teavitusüritusel! 

Lugupidamisega 

Prof Neeme Tõnisson 

Dr Peeter Padrik 

The workshop of the Nordic Society of Human Genetics and Precision Medicine took place in Tallinn

Estonia hosted NSHG-PM 2023 workshop “Precision Medicine: The Bridge from Research to Healthcare” on June 19-21. Neeme Tõnisson, activity leader of the EIT Health-supported BRIGHT project and Professor of Clinical Genetics at the Institute of Genomics / Estonian Biobank University of Tartu, took part in the round table discussion on polygenic risk scores in clinical applications. He also presented results from a number of studies involving genetic risk factors in Estonian Biobank participants, as well as in participants of the ongoing BRIGHT study.

The panelists Kristi Läll, Joeri Meijsen, Elisabeth Widen and Neeme Tõnisson established that when it comes to polygenic risk scores we are at the beginning of a long journey. It turned in to a lively discussion over current possibilities and limitations to using PRS as well as future potentials for further studies and methods in developing screening programmes. 

The Nordic region could potentially become a pilot for new uses of PRS because we have more data to use and the trust from the public in general. The Nordic Society of Human Genetics and Precision Medicine was created in order to establish a Nordic framework for research into the genetics of human diseases.

International study shows polygenic risk score results of genetics-based breast cancer precision prevention

The breast cancer genetic risk-based stratified screening service was introduced at the European Society of Human Genetics Conference: preliminary results of the EIT Health BRIGHT project in Estonia.

The purpose of the international BRIGHT project is to implement genetics-based breast cancer precision prevention in European healthcare moving beyond the current standard screening which is offered based on age only. Preliminary results revealed that genetics-based breast cancer precision prevention is feasible using multiple channels for the inclusion of women, including telemedicine solution with home-based genetic testing.

The project uses innovative polygenic risk score test AnteBC, which is developed by health technology company Antegenes, combined with traditional monogenic pathogenic variant testing, and implements different channels for population-based genetic screening.

This innovative approach is led by the BRIGHT consortium, which includes the University of Tartu, Antegenes, Tartu University Hospital, IESE Business School, GE Healthcare, Uppsala Region, Uppsala University Hospital, North Lisbon Central Hospital and Estonian Health Insurance Fund.

The Estonian arm of the project targeted women at age 35-49, which is the age before current standard screening, but among whom 20% of breast cancer cases concur. 800 women with a median age of 42 (range 35-49) were included to the project using 4 different channels: Antegenes’ online portal using home-based testing, pharmacies, a breast clinic, and a family physician service. Approximately 200 women were registered in each channel.

The women who participated in the study took the genetic test AnteBC to assess the polygenic predisposition to breast cancer. AnteBC PRS test can be adjusted to a specific population’s BC risk data and the standard mammography screening starting age. BC screening for younger women is initiated at a time when the predicted individual risk equals the average risk for women aged 50 years, thereby providing more equity.

Results of the polygenic risk score testing with AnteBC test revealed that 124 (15.5%) women had breast cancer risk higher than average risk at age 50. These women should start breast cancer screening already now. Monogenic pathogenic variant (BRCA1, BRCA2, etc) testing were specified using questionnaires according to official indications for these tests.

236 women (29.5%) responded to the feedback questionnaire, which revealed that 99.6% of respondents were glad that they had the opportunity to participate in the BRIGHT project and that the information contained for breast cancer precision screening was adequate, clear and understandable to 98.3% of participants. 11% of the women who participated in the project took the opportunity to receive an additional oral consultation after receiving the results, others felt that written detailed recommendations were sufficient. Feedback data is collected anonymously from study participants and healthcare professionals to assess the feasibility, acceptability, and healthcare system readiness of a stratified cancer screening approach.

The integration of breast cancer polygenic risk score testing and parallel monogenic variants management in healthcare aims to establish a stratified cancer screening approach that ensures better patient outcomes, improved equity, and increased screening participation rates. A similar project is still being conducted in Portugal and Sweden.

The BRIGHT project will result in a holistic personalized BC screening method to offer the best up-to-date clinical practice. It is applicable to all healthy women in the appropriate age group. Women can give a DNA sample during regular check-ups with their family doctor or even comfortably at home. All of this should increase the screening participation rates and reduce BC-caused deaths. The solution is already implemented in Estonian healthcare as an opportunistic breast cancer precision screening.

BRIGHT project has been supported by the European Commission via EIT Health BRIGHT innovation activity (project #220720). For more information about the BRIGHT clinical study and breast cancer risk-based stratified screening service, please visit https://brightscreening.eu.

BRIGHT Project Conference in Lisbon, Portugal

Conference „The Importance of Early Screening for Breast Cancer“

On May 15, a public event of the BRIGHT project about breast cancer in young women will take place in the Faculty of Medicine of the University of Lisbon. The event is aimed at the entire hospital community, key stakeholders in Portuguese healthcare, healthcare organizations, members of academia, patient associations, and the general public.

The purpose of the BRIGHT (Be RIGHT with breast cancer risk management) project is to test the channels and organization of the implementation of precision breast cancer screening based on genetic risks in the healthcare system of European countries. The goal is to identify a higher risk of breast cancer in young women who are still under 50 years old with a new genetic test. Based on the test results, it is possible to tailor screening and interventions according to that risk. The BRIGHT project is financed by EIT Health and the project takes place in Sweden, Portugal and Estonia.

Conference schedule:

14:30 Prof. Ana Paula Martins, Chairman of the Board of Directors – Opening of the Event

14:40 Prof. Luís Costa, Director Dpt. Oncology  – Breast Cancer in the Young Woman; a Portuguese Perspective 

15:00 Dr Peeter Padrik, CEO Antegenes – Development of breast cancer polygenic risk score test AnteBC and breast cancer precision prevention 

15:30 Prof. Neeme Tõnisson, Clinical Genetics, University of Tartu – Overview of BRIGHT project. How to approach the hereditary breast cancer in precision prevention? 

15:45 Q&A and Coffee Break 

16:00 Tamara Milagre, EVITA – Contribution to early-onset breast cancer prevention and research – Platform EVITA

16:15 Portuguese League Against Cancer – Breast Cancer Screening in Portugal 

16:35  Presentation of the Portuguese BRIGHT Project Team  

16:40 Q&A and Wrap Up 

The event is being recorded and can be viewed later here: http://youtube.com/@centrohospitalaruniversita80.

BRIGHT Information Day in Estonia

The BRIGHT information day, held on 9th of December at Park Inn by Radisson Meriton Conference & Spa Hotel, introduced the project and it’s novel objective to implement assessment of individual gentetic risk levels into breast cancer screening programs.

The event was attended by representatives from the Riigikogu Social Affairs Committee, Ministry of Social Affairs, Health Insurance Fund and National Institute for Health Development, members of patient organisations, professional associations and doctors in the field as well as by media representatives, research institutions and the wider public.

An international clinical study on breast cancer precision screening starts in Estonia 

Estonian women aged 35-49 can participate in the study “BRIGHT – Be RIGHT with breast cancer management”. The implementation study evaluates the use of a program of genetic risks based personalized breast cancer screening and prevention in Estonian, Swedish and Portuguese healthcare. The study is organized in Estonia by the University of Tartu, medical laboratory Antegenes and Tartu University Hospital. The Estonian Health Insurance Fund participates in the study as an external partner.  

The aim of the BRIGHT study is to test the channels and organization of the implementation of precision breast cancer screening based on genetic risks in the healthcare system of European countries. The study analyses a woman’s genetic predisposition to breast cancer, and based on this, personal medical recommendations and options for breast cancer prevention and early detection are provided. Women aged 35 to 49 years who have not had malignant tumors and who have not previously been tested for breast cancer predisposition based on the polygenic risk score can participate in the study. In Estonia, a total of 800 women can participate in the study. Participation in the study and accompanying health services are free of charge.  

Breast cancer is the most common malignant tumor among Estonian women and the cause of death due to tumors. To detect breast cancer as early as possible and reduce breast cancer mortality, mammographic screening is organized in Estonia for women aged 50–69 years.   

Breast cancer is curable if it’s detected early. “Unfortunately, breast cancer also occurs in younger women, but it is not practical to screen all of them in the same way. Breast cancer has a genetic predisposition, so a woman’s individual genetic breast cancer risk must be considered. That’s why genetic tests are used, with which we can find women with an elevated risk of breast cancer so that they can get to examinations on time,” explained Dr. Kristiina Ojamaa, head of the hematology-oncology clinic at the Tartu University Hospital.   

Oncologist Dr. Peeter Padrik, founder of the medical laboratory Antegenes, said that modern breast cancer prevention must be based on personal risk assessments, and not be done the same way for all women. “I’ve seen enough advanced breast cancers that are caught too late and cannot be cured. With precision breast cancer screening, we can change this situation. We have already developed a full breast cancer precision screening service that assesses both a woman’s polygenic risk and, if necessary, the presence of rare monogenic genes that increase the risk of breast cancer. In the BRIGHT study, together with our partners, we are testing the systematic use of this full service in Estonian healthcare and various channels through which we can involve women,” explained Padrik.  

If participating in the study, the woman will be given a novel genetic test AnteBC, developed by the Estonian medical laboratory Antegenes, to assess the polygenic predisposition to breast cancer. To perform the test, it is necessary to provide a simple and painless sample taken from the mouth with a cotton swab, from which DNA is extracted. With the AnteBC test, a woman’s personal genetic predisposition to the development of breast cancer is assessed, and based on this, recommendations are given at what age and how to start breast cancer mammographic screening. If the results indicate an increased risk, i.e. the need for screening, a digital referral is issued and the woman can participate in breast cancer early detection screening at the appropriate health facilities. In addition, the need for more comprehensive genetic testing by medical geneticists is specified. All tests and medical activities used in the BRIGHT study are health services recognized in Estonia and the European Union.  

“The BRIGHT study is an important project with which we help implement personalized medicine in Estonian healthcare and, on the other hand, take the knowledge to other parts of Europe and immediately test it in their healthcare setting. We actively invite women to join the study, because with your participation you will contribute to the wider adoption of personalized medicine both in Estonia and elsewhere in Europe,” said Dr. Neeme Tõnisson, professor of medical genetics at the University of Tartu, who is the lead researcher of the project.   

The Estonian Committee on Bioethics and Human Research has approved the study. Similar studies are also carried out in cooperation with partners in Sweden and Portugal. The study is supported by the European Commission through the EIT Health organization.  

How to participate in the study? Read more here: https://brightscreening.eu/osalemine/