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A conference abstract presented at the European Society for Medical Oncology (ESMO) 2025 meeting looks at prostate cancer screening in men with BRACA1 and BRACA2 mutations.
Prof Alastair D Lamb, CRUK Advanced Clinician Scientist Fellow, Barts Cancer Institute, Queen Mary University of London (QMUL), said:
Is this good quality research? Are the conclusions backed up by solid data?
“Yes, and from it’s a highly reputable group, led by Ros Eeles”.
How does this work fit with the existing evidence?
“Complementary, useful advance.”
Have the authors accounted for confounders? Are there important limitations to be aware of?
“I’m unable to tell from an abstract.”
What are the implications in the real world? Is there any overspeculation?
“Germline genetic risk scoring is being trialled in the recently commissioned TRANSFORM Trial (£42M from PCUK and NIHR) and this data on BRCA 1 and 2 gives us confidence of possible role for these tests in prostate cancer screening.”
How strong is the link between being BRCA1/2 gene carrier and developing prostate cancer?
“The key thing is not the link with developing prostate cancer as most prostate cancer is harmless. The exciting detail in this study is that the presence of a BRCA mutation increased the proportion of NCCN higher risk prostate cancer from 31% of diagnoses to 64%. This is critical. We don’t want just to diagnose more indolent prostate cancers!”
Does this study offer enough evidence to roll out screening in carriers of these mutations at the national level?
“See above. No definitely insufficient evidence to rollout screening nationwide but potentially in a targeted fashion to those already known to have DNA repair defect (DDR) mutations (such as BRCA1 and 2). Yes, there is definitely a risk of creating a population of “worried well” through this work. It’s not so much false positive and false negatives because that assumes we have some kind of binary test. It’s all a spectrum of risk.
“We await the full publication to be able to fully scrutinize the data. Tentatively excited though!”
Professor Hashim Ahmed, Chair of Urology at Imperial College London, said:
“This study reinforces evidence that men with mutations in the BRCA1 and BRCA2 genes have a higher risk of prostate cancer and might benefit from targeted screening.
“Only an estimated 1 in 260 men have these mutations, so identifying them is a key logistical challenge. Family history is not recorded routinely in primary care databases, so we have to rely on awareness campaigns to encourage men with a family history to come forward to get tested for BRCA mutations.
“Such campaigns, if not handled carefully, could lead a huge increase in untargeted prostate cancer screening, which carries issues. If this occurred, the healthcare system would be overwhelmed and we might have all the issues of harms of wider screening.”
Prof James Catto, Professor of Urology, University of Sheffield, said:
“The results appear compelling. Men with genetic mutations of the BRCA1 and BRCA2 genes are more likely to get prostate cancer, more likely to get aggressive cancer and to get it at a younger age than the general population. Given this is a small proportion of the population, it seems very sensible to start testing these men in their 40s with PSA blood tests.”
Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said:
“The abstract is an update from the IMPACT study and it is based on a body of research over the last decade or two, that associate pathogenic variants (mutations) of BRCA2 with a higher and earlier incidence of prostate cancer. A recent study (DOI: 10.1200/JCO.21.02112) showed that mutations in BRCA2 double the risk of developing prostate cancer by the age of 80. BRCA2 and BRCA1 are involved in several cellular processes, the most important being DNA damage repair mechanisms. BRCA2 is critical for one of these mechanisms, called Homology Recombination, that ensures accurate error-free repair of the most serious type of DNA damage, which involves breakage of both strands of the DNA. Without this mechanism working properly or at all, cells will be able to survive and replicate with an accumulating mutation burden, that makes them more likely to become pathogenic.
“Early detection of cancerous growth is fundamental for an effective and successful treatment and therefore any tools to improve accuracy and sensitivity of diagnosis is a significant medical advance. Testing for Prostate-Specific Antigen (PSA) is a good tool for diagnosis and follow-up of prostate cancer, but what is proposed is to target specifically men carrying mutations in BRCA2 and perhaps BRCA1 for early and more regular testing. This however, jumps over the fact that in order to do this, it will be necessary to screen for mutations in these genes in the first place. This could be done at a population level using molecular and genetic tools but these are more complex than the blood test used to detect PSA. The benefit of such an approach is that men at higher risk of developing prostate cancer could be diagnosed earlier and have a better chance of recovery. It must not be overlooked that not all men developing prostate cancer present mutations in BRCA2, so the rationale for the deployment of diagnostic tools needs to take into consideration all the risks and the wider population.”
Mr Ben Lamb, Consultant Urological and Robotic Surgeon, Barts Health and UCLH NHS Trusts, and Clinical Senior Lecturer, Barts Cancer Institute, Queen Mary University of London (QMUL), said:
How does this work fit with the existing evidence?
“This work is consistent with current understanding of increased prostate cancer risk in BRCA gene carriers with earlier diagnosis and more aggressive disease.”
Have the authors accounted for confounders? Are there important limitations to be aware of?
“This is an international study, but it would be interesting to look at the inclusion of different ethnic groups, especially those known to be at higher risk e.g. black men. Are other risk factors balanced e.g. obesity, age etc.?”
What are the implications in the real world? Is there any overspeculation?
“BRCA gene carriers should be made aware of increased risk of prostate cancer, but the optimal risk assessment protocol is not known, and this study is not designed to specify this.
“Prospective randomised trial of the optimal case finding/screening method are needed, such as TRANSFORM, however, BRCA carriers are a minority of the population, so they may not be well represented and findings may not be entirely applicable.
“More data is needed to understand how many BRCA carriers are identified in populations around the world and how accessible testing is. GP records of BRCA status are not well understood and may not be a reliable means of finding cases needed to implement a screening program.”
How strong is the link between being BRCA1/2 gene carrier and developing prostate cancer?
“The link between BRCA genes and prostate cancer is well established, risk of BRCA 2 is thought to be at least double population risk, with BRCA 1 being less strongly predictive but still higher than population background risk.”
Does this study offer enough evidence to roll out screening in carriers of these mutations at the national level?
“Population screening for prostate cancer remains controversial as historically the harms of over diagnosis and over treatment for a very common cancer that does not always cause harm, have been finely balanced with the benefits of early detection and treatment. Recently, evidence seems to be emerging that with modern pathways, the benefits outweigh the risks. Case finding amongst high-risk groups is a related but different approach to population screening. BRCA mutations are uncommon, and may be poorly coded in GP records, but the risk of cancer among carriers is higher. targeted testing would need to be coupled with improved means of detecting and recording BRCA mutation status.”
“It will be important to see the full study published prior to enacting policy or practice change.”
The conference abstract ‘The IMPACT study into prostate cancer screening in those with BRCA1 and BRCA2 gene mutations’ by R Eeles et al. was presented at European Society for Medical Oncology (ESMO) 2025 meeting. The embargo on the abstract lifted at 00:01 UK TIME on Friday 17 October 2025.
Declared interests
Prof Alastair Lamb: Know Ros Eeles well (and many of the other IMPACT authors). I am a member of the Pan Prostate Cancer Group which she leads. My lab work on a very similar area but with somatic rather than germline genetics in prostate cancer. I have also conducted trials in prostate cancer and am or have been an investigator / lead investigator on ELIPSE (NIHR), TRANSLATE (NIHR), PART (NIHR), PROMOTE (CRUK), TROMBONE (PCF). I am funded by Cancer Research UK with an Advanced Clinician Scientist Fellowship to investigate prostate cancer risk. I am also funded by The Bob Champion Cancer Trust & UCARE. I was invited by Prostate Cancer Research & Soho House to attend the screening meeting at Houses of Parliament earlier this week, Tuesday 24th October 2025
Dr Alena Pance: I declare I do not have any conflict of interest regarding this work.
For all other experts, no reply to our request for DOIs was received.