Prof Ranjit Manchanda MD, MRCOG, PhD Professor of Gynaecological Oncology & Consultant Gynaecological Oncologist

Population Based BRCA-Testing Can Detect More Breast and Ovarian Cancers, and Be Cost-Effective

MedicalResearch.com Interview with:

Prof Ranjit Manchanda MD, MRCOG, PhD Professor of Gynaecological Oncology & Consultant Gynaecological Oncologist

Prof. Manchanda

Prof Ranjit Manchanda MD, MRCOG, PhD
Professor of Gynaecological Oncology & Consultant Gynaecological Oncologist
NHS Innovation Accelerator (NIA) Fellow
Integrated Academic Training Programme Director
London Specialty School of Obstetrics & Gynaecology, Health Education England
Specialty Research Lead for Gynaecological Cancer, NIHR, North Thames Clinical Research Network
Cancer Research UK, Barts Centre | Queen Mary University of London
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine | Charterhouse Square | London
Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital

MedicalResearch.com: What is the background for this study?

Response: Around 10–20% of ovarian cancers and 6% breast cancers overall are caused by inheritable BRCA1/BRCA2 mutations. Women carrying BRCA1/BRCA2 mutations have a 17–44% risk of ovarian cancer and 69–72% risk of breast cancer until age 80 years. Most of these cancers can be prevented in unaffected BRCA1/BRCA2 women carriers. Women can opt for a range of options including screening, preventive, and reproductive choices to minimise their risk.

The current approach uses established clinical-criteria/family-history (FH) based a priori BRCA probability thresholds to identify high-risk individuals eligible for BRCA testing. However, this requires individuals and health practitioners to recognise and act on a significant FH. BRCA carriers, who are unaware of their FH, unappreciative of its risk/significance, not proactive in seeking advice, or lack a strong FH (small families/paternal inheritance/chance) get excluded. Over 50% BRCA carriers do not fulfil clinical criteria and are missed.

Despite >25 years of BRCA testing and effective mechanisms for prevention, current guidelines and access to testing pathways remain complex and associated with a massive under-utilisation of genetic testing. Only 20% of eligible women have accessed/undergone genetic testing and our earlier analysis showed that 97% of BRCA carriers in the population remain unidentified. Current detection rates are inadequate to identify all BRCA carriers and even doubling detection rates will not work.

Why should we wait for decades for people to develop cancer before identifying BRCA carriers and unaffected at-risk family members to offer prevention?. This highlights substantial missed opportunities for early detection and prevention. A new population testing approach can change this. Jewish population studies show this is feasible, acceptable, has high satisfaction (91–95%), significantly reduces anxiety, doesn’t harm psychological well-being or quality of life, and is extremely cost-effective. However, this has not been evaluated in the general population and in particular across different  countries or health systems. The potential applicability and scope for this approach transcends continents and countries. Additionally, for interventions to be sustainable, they need to be cost-effective and affordable.

We have undertaken a cost-effectiveness analysis of population based BRCA testing compared with current standard clinical testing of women designated as high risk, across high income countries (UK/USA/Netherlands), upper-middle income countries (China/Brazil), and low-middle income country (India).

MedicalResearch.com: What are the main findings?
 

Response: We found that found that population based testing was extremely cost effective in high and upper middle income countries from a payer perspective. From a societal perspective it was cost saving in high income countries and cost effective in middle income countries like China and Brazil. Costs of BRCA testing would need to fall to around USD $172 to become cost effective in low income countries like India

Findings suggest that population based BRCA testing can prevent an additional 2,319-2,666 breast cancer and 327-449 ovarian cancer cases per million women than the current clinical strategy. The table below shows the number of cancer cases and deaths that would be prevented over a lifetime if genetic testing was offered to the entire population

  Breast cancer Ovarian cancer
Cases prevented Deaths prevented Cases prevented Deaths prevented
UK 57,708 5,941 9,727 5,919
USA 269,089 17,446 43,817 24,343
Netherlands 15,181 1,424 2,557 1,509
China 1,050,314 121,353 154,756 87,103
Brazil 156,299 30,509 25,170 15,724
India 692,571 177,697 97,659 77,948

 

We have undertaken extensive scenario and sensitivity analyses to support these findings.

MedicalResearch.com: What should readers take away from your report?

Response: General population BRCA testing can bring about a new paradigm for improving global cancer prevention. This approach can prevent hundreds of thousands more cancers than the current clinical strategy and is cost-effective. Why do we need to wait for people to develop a preventable cancer to identify others in whom we can prevent cancer? Strategies and pathways for population testing must be developed to enable population genomics to achieve its potential for maximising early detection and cancer prevention.

Our findings are important, as we show that a new population-based approach can have much broader global applicability and a far greater impact on breast and ovarian cancer burden in the population than current treatment strategies.

With the costs of testing falling this can provide huge new opportunities for cancer prevention and changes in the way we deliver cancer genetic testing. This approach can ensure that more women can take preventative action to reduce their cancer risk or undertake regular screening.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: There is an urgent need for multiple real world implementation studies across countries for evaluating general population BRCA testing and to develop local/regional/country and context-specific implementation pathways. These studies will need to provide prospective data on the impact of population testing on psychological well-being, quality of life, long-term health behaviour, socio-ethics, and lifestyle outcomes. Challenges and logistic hurdles which will need addressing include workforce expansion/upskilling, increasing public and health-professional awareness, establishing/expanding laboratory testing infrastructure, expanding downstream management pathways, and involving general practitioners, genetics services, gynaecologists, and breast clinicians/services.

A framework/structure for data management and legal and regulatory protections will need to be established. These changes will need to be system/country and context-specific. 

Disclosures: The study is study was supported by the NHS Innovation Accelerator Fellowship and the women’s cancer charity The Eve Appeal.

This research was an international collaboration involving research teams from Queen Mary University of London (UK), London School of Hygiene & Tropical Medicine (UK), Amsterdam UMC, Vrije Universiteit Amsterdam (Netherlands); Universidade de Sao Paulo, Sao Paulo (Brazil); Peking University, Beijing (China); Indian Institute of Technology, Kharagpur (India); Presidency University (Kolkata), Tata Medical Centre, Kolkata (India); University of Melbourne, Victoria (Australia); Newcastle University (UK).

 

Citation:

Manchanda, R.; Sun, L.; Patel, S.; Evans, O.; Wilschut, J.; De Freitas Lopes, A.C.; Gaba, F.; Brentnall, A.; Duffy, S.; Cui, B.; Coelho De Soarez, P.; Husain, Z.; Hopper, J.; Sadique, Z.; Mukhopadhyay, A.; Yang, L.; Berkhof, J.; Legood, R. Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems. Cancers 202012, 1929.

https://www.mdpi.com/2072-6694/12/7/1929#cite

 

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Jul 22, 2020 @ 1:10 am

 

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