On 25 November, the preliminary results of the Portuguese study were presented at the BRIGHT seminar at ULS Santa Maria Hospital in Lisbon as part of the Santa Maria Innovation Days.

The Portuguese clinical study was initiated in June 2023, with the majority of participants recruited between January and July 2024. A total of 793 PRS reports were generated for women aged 35–49.

The recruitment process in Portugal took place in two stages. The first stage, launched in June 2023, targeted hospital staff. The second stage began in December 2023 and was promoted through social media, the hospital’s website, local media, and digital screens throughout the hospital (MUPIs). Over 1,000 volunteers expressed interest in participating, and 800 women ultimately took part in the testing.

In Portugal, enrolment took place at the hospital in an appointment-style format. Volunteers either self-administered the PRS test or received assistance from a nurse, followed by a thorough clinical examination with an oncologist. The participants were tested using the AnteBC test, with buccal swab samples sent to Antegenes for processing. Once analysed, a PRS report, medical assessment, and clinical recommendations were generated, and results were provided to participants. The women were categorised into three risk groups: low (RR < 1.5), slightly elevated (1.5 ≤ RR < 2.7), and elevated (RR > 2.7).

The results showed that the average participant age was 41, with an average cohort percentile of 50.68%. The majority of women (585, or 73.77%) had a 10-year risk at or below the average risk for a 50-year-old woman, while 208 women (26.23%) had a 10-year risk higher than the average for 50-year-old women in Portugal. Based on the recommendations, 390 women were advised to begin mammographic screening before the age of 50, and 193 women (24%) were recommended to start screening within the current year due to their elevated risk score.

Additionally, all participants were offered a follow-up mammogram and breast ultrasound after their first appointment. Almost half of the volunteers underwent both ultrasound (390) and mammography (48%). The most common reasons for not undergoing imaging exams were pregnancy or recent motherhood.

Finally, the first participant feedback questionnaire revealed that most volunteers (32.4%) first heard about the project through a family member or friend, while 28% learned about it from their doctor. The study information was considered sufficient, clear, and understandable by 89% of participants. Moreover, 98.6% of women were pleased to have participated and would make the same choice again.

At the 1st International Conference on Young Women’s Breast Cancer and Health in Lisbon in October 2024, Prof Neeme Tõnisson presented the results of the BRIGHT Estonian arm. Additionally, two posters, “Genetic Risk-Based Breast Cancer Screening Service Model for Younger Women in Estonia” and “Epidemiological and Radiologic Factors in the Portuguese BRIGHT Study Cohort – Preliminary Results,” were presented by the BRIGHT Consortium partners.

October is recognised as Breast Cancer Awareness Month, dedicated to raising awareness about breast cancer prevention. The month concluded with a significant event—the 1st International Conference on Young Women’s Breast Cancer and Health in Lisbon. Representing Estonia, Prof. Neeme Tõnisson presented the genetic risk-based personalised breast cancer prevention approach developed, researched, and clinically implemented through the EIT Health BRIGHT project in Estonia. His presentation was titled: “BRIGHT International Consortium Project: Polygenic Risk Score in Early Breast Cancer Detection”.

Breast cancer is, unfortunately, becoming the most common cancer globally, with incidence rates increasing, including among younger women. However, the positive news is that the likelihood of developing breast cancer can be reduced by addressing risk factors, and, with timely detection, it can be treated successfully.

It was inspiring to witness discussions at the conference, particularly from women’s and patient organisations, highlighting that for effective breast cancer prevention and early detection, women need to understand their personal risk levels. Healthcare professionals must also provide personalised prevention guidelines tailored to these risks.

The BRIGHT clinical study in Estonia, conducted by the University of Tartu, Antegenes, and Tartu University Hospital, confirms the feasibility and acceptability of polygenic risk score-based breast cancer screening from the perspectives of both participating women and healthcare professionals. The application of polygenic risk scores significantly enhances the assessment of genetic predisposition to cancer and modernises cancer prevention through personalisation in Estonia and other European countries.

Despite current screening programmes and personalised treatment approaches, breast cancer remains the most common malignant tumour among women and the leading cause of cancer-related deaths worldwide, including in Estonia.

The current screening programme considers only age and female sex as risk factors, yet women’s breast cancer risks vary significantly due to multiple factors, including genetic predisposition. In Estonia, screening begins at the age of 50, but one in five breast cancer cases occurs in younger women who may never reach the screening age. At the same time, the balance of benefits and challenges of including all younger women in the screening programme is insufficient to justify, and doing so would also incur excessive costs.

The aim of the international BRIGHT (Be RIGHT with breast cancer risk management) study, launched in 2022, was to assess the feasibility of personalised breast cancer screening based on genetic risk in women under the age of 50. This involved using the polygenic risk score (PRS) genetic test AnteBC, developed by the Estonian company Antegenes, as well as testing for monogenic pathogenic variants (MPVs) in local laboratories and the personalised medicine clinic at Tartu University Hospital. The study also evaluated the acceptability and satisfaction of this service model among both women and healthcare professionals.

The BRIGHT results in Estonia

In Estonia, 800 healthy women aged 35–49 were enrolled in the study between October 2022 and July 2023, either through the web portal, Breast Clinic, pharmacy, or primary healthcare centre. Participants received pre-test information and signed informed consent forms. Buccal swab samples were collected for DNA analysis, and participants completed two questionnaires on family cancer history and breast cancer clinical risk factors. One participant did not complete the questionnaires and was excluded from the analysis, resulting in a study cohort of 799 women with a median age of 40.

Before the clinical pilot study commenced in Estonia, several training sessions were conducted for the investigator groups.

Polygenic risk score (PRS) testing was performed for all participants using the AnteBC test (by Antegenes, Estonia).

• 469 (58.7%) of the participants had the same or lower breast cancer risk compared to the average risk in Estonia at the age of 50.
• A total of 330 (41.3%) were identified as having elevated polygenic breast cancer risk.
• Among these, 307 (38.4%) received recommendations to begin breast cancer screening before the age of 50.
• Of the 307 women, 124 (40.4%) were advised to start mammography screening in the current year and received referral notes.

By the time the study database was closed:

• 93 (75.0%) of the 124 women had undergone mammograms, resulting in one diagnosis of a precancerous lesion and one diagnosis of carcinoma in situ.
• Out of the 799 women, 90 (11.3%) registered for post-test polygenic risk consultations.

Based on the family cancer history questionnaire:

• 152 (19.0%) women were referred to a clinical geneticist.
• Of these, 99 (65.1%) attended appointments, and 90 completed monogenic pathogenic variant (MPV) testing.
• Four (4.4%) women tested positive for MPV, with one of these women also having elevated polygenic risk.
• All participants who underwent MPV testing received post-test genetic counselling.

Participant Feedback:
The response rate for the first feedback questionnaire was 30.0%, and for the second, 31.9%. Participants reported:

• Satisfaction with telemedicine solutions.
• Sufficient, clear, and understandable study information.
• Intent to follow the provided recommendations and the ability to manage knowledge of their genetic risks.
• Almost all participants (99.6%) were glad to have participated in the study and would make the same choice again.

Healthcare Professional Feedback:
The response rate for the healthcare professionals’ feedback questionnaire was 56.3%. Key findings include:

• 38.9% of respondents were unfamiliar with PRS testing before the study but found the pre-study training sufficient.
• Most (88.9%) considered genetic risk assessment important for breast cancer prevention.
• 83.3% expressed willingness to use breast cancer PRS testing in their clinical practice.

A cost-effectiveness analysis demonstrated that implementing this polygenic risk score-based model can prevent 15 breast cancer-related deaths per 10,000 women and is likely to be a good investment in public funding. Based on the findings of this study, it is recommended to integrate telemedicine solutions into the screening service model for both participant engagement and DNA sample collection. Such an approach makes breast cancer screening more accessible and cost-efficient, thereby improving breast cancer prevention and early detection.

In parallel, clinical studies under the BRIGHT project are ongoing in Sweden and Portugal, with approximately 800 women enrolled in each country. To support the implementation of risk-based breast cancer screening, a model analysis of this method is conducted in each country, including clinical benefits and cost-effectiveness assessments. The study is funded by the European Commission through the EIT Health organisation.

BRIGHT Consortium partners from Tartu University Hospital presented the results of the Estonian arm at the ESMO Congress 2024 in Barcelona, Spain. An abstract titled “The feasibility of polygenic risk score-based population screening for breast cancer: The experience from the BRIGHT study in Estonia” was presented by Anni Lepland.

One-fifth of breast cancer cases occur in women under the age of 50. Across Europe, the current challenge is that women under 50 are not typically screened for breast cancer. However, women at increased risk should begin screening earlier.

The Estonian branch of the BRIGHT consortium introduced a new service model for genetic risk-based screening. This model incorporates clinical-grade polygenic risk score testing for all women. Those identified as high risk are referred for additional screening, with the start and frequency of mammograms tailored to individual risk. The service also includes consultations with medical geneticists and single-gene testing for women with a family history of cancer.

Feedback from participants and healthcare professionals has been positive. The study also confirmed that personalised breast cancer screening can effectively involve women through multiple channels, including online telemedicine, GP practices, breast clinics, and pharmacies.

On Monday, April 22nd, a seminar titled “Breast Cancer Precision Prevention – Presenting Results from Sweden, Estonia and Portugal” was held at 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 years 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 a 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-effectiveness of precision breast cancer prevention is evaluated.

Preliminary 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 lead for the study in Region 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, Dr. Filipa Sampaio, health economist at Region Uppsala, gave a presentation titled “Cost-effectiveness analysis of a polygenic risk-tailored breast cancer screening – the BRIGHT project experience”, highlighting preliminary results for the Swedish setting. The cost-effectiveness analysis examined the potential costs and benefits of 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, a scenario where women at low risk would commence screening at a later stage than currently recommended was also assessed.

Inna Feldman, project leader from Region Uppsala, highlighted the results from the follow-up survey. Feedback was collected from all participants, resulting in a response rate of 60%. “92% of respondents indicated that they were glad that 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 mammograms before screening. However, regular self-examination was not common among participants, especially among 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 is 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 organisations, 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 emphasised the need to present the results to politicians and decision-makers.

Kim Höglund from the Uppsala Breast Cancer Association emphasised 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 peer-reviewed scientific journals. 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^th, a BRIGHT open seminar will take place in Portugal, where the initial results of the pilot study and preliminary cost-effectiveness analysis results in the Portuguese setting 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.

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

Hea Kolleeg! 

Olete väga oodatud BRIGHT projekti teavitusüritusele – kliinilise uuringu tulemused Eestis ja patsiendikäsitlus, mis toimub kolmapäeval, 8. novembril kl 15.00–17.00 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 

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.

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.