Half of the people tested were unaware of their genetic risk for contracting the disease
Existing clinical laboratory genetic screening guidelines may be inadequate when it comes to finding people at risk of hereditary breast-ovarian cancer syndromes and Lynch syndrome (aka, hereditary nonpolyposis colorectal cancer). That’s according to a study conducted at the Mayo Clinic in Rochester, Minn., which found that about half of the study participants were unaware of their genetic predisposition to the diseases.
Mayo found that 550 people who participated in the study (1.24%) were “carriers of the hereditary mutations.” The researchers also determined that half of those people were unaware they had a genetic risk of cancer, and 40% did not meet genetic testing guidelines, according to a Mayo Clinic news story.
The discoveries were made following exome sequencing, which the Mayo Clinic news story described as the “protein-coding regions of genes” and the sites for most disease-causing mutations.
“Early detection of genetic markers for these conditions can lead to proactive screenings and targeted therapies, potentially saving lives of people and their family members,” said lead author Niloy Jewel Samadder, MD, gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center.
“This study is a wake-up call, showing us that current national guidelines for genetic screenings are missing too many people at high risk of cancer,” said lead author Niloy Jewel Samadder, MD (above), gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center. New screening guidelines may increase the role of clinical laboratories in helping physicians identify patients at risk of certain hereditary cancers. (Photo copyright: Mayo Clinic.)
Advancing Personalized Medicine
“The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC (hereditary breast and ovarian cancer) and LS (Lynch syndrome),” the authors wrote in JCO Precision Oncology.
For the current study, Helix, a San Mateo, Calif. population genomics company, collaborated with Mayo Clinic to perform exome sequencing on the following genes:
BRCA1 and BRCA2 genes (hereditary breast and ovarian cancer).
Mayo/Helix researchers performed genetic screenings on more than 44,000 study participants. According to their published study, of the 550 people who were found to have hereditary breast cancer or Lynch syndrome:
387 had hereditary breast and ovarian cancer (27.2% BRCA1, 42.8% BRCA2).
163 had lynch syndrome (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM).
Participants recruited by researchers hailed from Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla.
Minorities were less likely to meet the NCCN criteria than those who reported as White (51.5% as compared to 37.5%).
“Our results emphasize the importance of expanding genetic screening to identify people at risk for these cancer predisposition syndromes,” Samadder said.
Exome Data in EHRs
Exomes of more than 100,000 Mayo Clinic patients have been sequenced and the results are being included in the patients’ electronic health records (EHR) as part of the Tapestry project. This gives clinicians access to patient information in the EHRs so that the right tests can be ordered at the right time, Mayo Clinic noted in its article.
“Embedding genomic data into the patient’s chart in a way that is easy to locate and access will assist doctors in making important decisions and advance the future of genomically informed medicine.” said Cherisse Marcou, PhD, co-director and vice chair of information technology and bioinformatics in Mayo’s Clinical Genomics laboratory.
While more research is needed, Mayo Clinic’s accomplishments suggest advancements in gene sequencing and technologies are making way for data-driven tools to aid physicians.
As the cost of gene sequencing continue to fall due to improvement in the technologies, more screenings for health risk factors in individuals will likely become economically feasible. This may increase the role medical laboratories play in helping doctors use exomes and whole genome sequencing to screen patients for risk of specific cancers and health conditions.
These advances in the battle against cancer could lead to new clinical laboratory screening tests and other diagnostics for early detection of the disease
As Dark Daily reported in part one of this story, the World Economic Forum (WEF) has identified 12 new breakthroughs in the fight against cancer that will be of interest to pathologists and clinical laboratory managers.
As we noted in part one, the WEF originally announced these breakthroughs in an article first published in May 2022 and then updated in October 2024. According to the WEF, the World Health Organization (WHO) identified cancer as a “leading cause of death globally” that “kills around 10 million people a year.”
The WEF is a non-profit organization base in Switzerland that, according to its website, “engages political, business, academic, civil society and other leaders of society to shape global, regional and industry agendas.”
Monday’s ebrief focused on four advances identified by WEF that should be of particular interest to clinical laboratory leaders. Here are the others.
Personalized Cancer Vaccines in England
The National Health Service (NHS) in England, in collaboration with the German pharmaceutical company BioNTech, has launched a program to facilitate development of personalized cancer vaccines. The NHS Cancer Vaccine Launch Pad will seek to match cancer patients with clinical trials for the vaccines. The Launch Pad will be based on messenger ribonucleic acid (mRNA) technology, which is the same technology used in many COVID-19 vaccines.
The BBC reported that these cancer vaccines are treatments, not a form of prevention. BioNTech receives a sample of a patient’s tumor and then formulates a vaccine that exposes the cancer cells to the patient’s immune system. Each vaccine is tailored for the specific mutations in the patient’s tumor.
“I think this is a new era. The science behind this makes sense,” medical oncologist Victoria Kunene, MBChB, MRCP, MSc (above), trial principal investigator from Queen Elizabeth Hospital Birmingham (QEHB) involved in an NHS program to develop personalized cancer vaccines, told the BBC. “My hope is this will become the standard of care. It makes sense that we can have something that can help patients reduce their risk of cancer recurrence.” These clinical trials could lead to new clinical laboratory screening tests for cancer vaccines. (Photo copyright: Queen Elizabeth Hospital Birmingham.)
Seven-Minute Cancer Treatment Injection
NHS England has also begun treating eligible cancer patients with under-the-skin injections of atezolizumab, an immunotherapy marketed under the brand name Tecentriq, Reuters reported. The drug is usually delivered intravenously, a procedure that can take 30 to 60 minutes. Injecting the drug takes just seven minutes, Reuters noted, saving time for patients and cancer teams.
The drug is designed to stimulate the patient’s immune system to attack cancer cells, including breast, lung, liver, and bladder cancers.
AI Advances in India
One WEF component—the Center for the Fourth Industrial Revolution (C4IR)—aims to harness emerging technologies such as artificial intelligence (AI) and virtual reality. In India, the organization says the Center is seeking to accelerate use of AI-based risk profiling to “help screen for common cancers like breast cancer, leading to early diagnosis.”
Researchers are also exploring the use of AI to “analyze X-rays to identify cancers in places where imaging experts might not be available.”
Using AI to Assess Lung Cancer Risk
Early-stage lung cancer is “notoriously hard to detect,” WEF observed. To help meet this challenge, researchers at Massachusetts Institute of Technology (MIT) developed an AI model known as Sybil that analyzes low-dose computed tomography scans to predict a patient’s risk of getting the disease within the next six years. It does so without a radiologist’s intervention, according to a press release.
Using Genomics to Identify Cancer-Causing Mutations
In what has been described as the “largest study of whole genome sequencing data,” researchers at the University of Cambridge in the UK announced they have discovered a “treasure trove” of information about possible causes of cancer.
Using data from England’s 100,000 Genomes Project, the researchers analyzed the whole genome sequences of 12,000 NHS cancer patients.
This allowed them “to detect patterns in the DNA of cancer, known as ‘mutational signatures,’ that provide clues about whether a patient has had a past exposure to environmental causes of cancer such as smoking or UV light, or has internal, cellular malfunctions,” according to a press release.
The researchers also identified 58 new mutational signatures, “suggesting that there are additional causes of cancer that we don’t yet fully understand,” the press release states.
The study appeared in April 2022 in the journal Science.
Validation of CAR-T-Cell Therapy
CAR-T-cell therapy “involves removing and genetically altering immune cells, called T cells, from cancer patients,” WEF explained. “The altered cells then produce proteins called chimeric antigen receptors (CARs), which can recognize and destroy cancer cells.”
The therapy appeared to receive validation in 2022 when researchers at the University of Pennsylvania published an article in the journal Nature noting that two early recipients of the treatment were still in remission after 12 years.
However, the US Food and Drug Administration (FDA) announced in 2023 that it was investigating reports of T-cell malignancies, including lymphoma, in patients who had received the treatment.
WEF observed that “the jury is still out as to whether the therapy is to blame but, as a precaution, the drug packaging now carries a warning.”
Breast Cancer Drug Repurposed for Prevention
England’s NHS announced in 2023 that anastrozole, a breast cancer drug, will be available to post-menopausal women to help reduce their risk of developing the disease.
“Around 289,000 women at moderate or high risk of breast cancer could be eligible for the drug, and while not all will choose to take it, it is estimated that if 25% do, around 2,000 cases of breast cancer could potentially be prevented in England, while saving the NHS around £15 million in treatment costs,” the NHS stated.
The tablet, which is off patent, has been used for many years to treat breast cancer, the NHS added. Anastrozole blocks the body’s production of the enzyme aromatase, reducing levels of the hormone estrogen.
Big Advance in Treating Cervical Cancer
In October 2024, researchers announced results from a large clinical trial demonstrating that a new approach to treating cervical cancer—one that uses currently available therapies—can reduce the risk of death by 40% and the risk of relapsing by 36%.
“This is the biggest improvement in outcome in this disease in over 20 years,” said Mary McCormack, PhD, clinical oncologist at the University College London and lead investigator in the trial.
The scientists published their findings in The Lancet.
Pathologists and clinical lab managers will want to keep track of these 12 breakthrough advancements in the diagnosis and treatment of cancer highlighted by the WEF. They will likely lead to new screening tests for the disease and could save many lives.
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
Findings could lead to new clinical laboratory cancer screening tests for BRCA1 and BRCA2 among specific population regions
Descendants of a remote Scottish island are much more likely to carry a cancer-causing BRCA2 gene than the rest of the UK. That’s according to a study conducted by the University of Edinburgh in Scotland. For pathologists and clinical laboratory managers, the study’s findings demonstrate how ongoing research into the genetic makeup of subpopulations will find groups that have higher risk for specific health conditions than the general population. Thus, diagnosticians can pay closer attention to screening these groups to achieve early diagnosis and intervention.
“The findings follow earlier research from the Viking Genes study that found a cancer-causing variant in the related BRCA1 gene, common among people from Orkney [a group of islands off Scotland’s northern coast],” noted a University of Edinburgh news release.
In their latest research, the genetic scientists discovered that the BRCA2 gene can be found in one in every 40 people with heritage from the island of Whalsay in Scotland’s Shetland island group. This gene is one of the most common genes that can be linked to breast cancer and ovarian cancer in women and breast and prostate cancer in men.
Those who inherit the BRCA2 gene have a significantly higher risk of developing certain cancers than the general population. For example, according to the National Cancer Institute, more than 60% of women who inherit the gene will develop breast cancer in their lifetimes.
The volunteers in the Viking Genes study have a risk of having a BRCA2 gene that is 130 times higher than the general UK population. According to the BBC, geneticists believe the gene can be traced back to one family from the island of Whalsay before 1750.
“It is very important to understand that just two gene changes account for more than 90% of the inherited cancer risk from BRCA variants in Orkney and Shetland. This is in stark contrast to the situation in the general UK population, where 369 variants would need to be tested to account for the same proportion of cancer risk from BRCA genes. Any future screening program for the Northern Isles should therefore be very cost-effective,” said James Wilson, DPhil, FRCPE (above), Professor of Human Genetics at University of Edinburgh and leader of the study, in a news release. Clinical laboratories in the UK will be involved in those screenings. (Photo copyright: Scottish Genomes Partnership.)
Early Diagnosis Brings Hope to Families
The UK’s National Health Service (NHS) offers genetic testing to relatives of people with a known BRCA variant. Individuals with at least one Whalsay grandparent, and who have a close family history of breast, ovarian, or prostate cancer, can also request NHS testing.
As the BBC reported, University of Edinburgh’s discovery has given families answers and hope for the future. Individuals who fit the criteria for being at risk of inheriting the BRCA gene can narrow their testing and work more specifically on preventative measures with their doctors.
Christine Glaser, a woman from Lerwick in Shetland, learned she carried the BRCA gene after participating in the study. Though the Viking genes research took place nearly a decade ago, scientific understanding of genes has improved allowing geneticists to draw new conclusions from previous studies.
Although Glaser lost her sister to ovarian cancer, she and her family were unaware of their heightened genetic risk.
“I got offered preventative measures so I could get my ovaries removed and I could get a mastectomy. So, that’s what I did … when I got my ovaries removed, they checked them and there was no cancer, but then I had a mammogram and they found cancer,” she told the BBC. Glaser’s cancer was successfully treated thanks to early detection.
Closing Gap in Genetic Testing
“This BRCA2 variant in Whalsay I think arose prior to 1750. This is why these things become so common in given places because many people descend from a couple quite far back in the past, and if they have a cancer variant, then a significant number of people today—five or even 10 generations later—will have it. This is true everywhere in Scotland, it’s just magnified in these small places,” said James Wilson, DPhil, FRCPE, Professor of Human Genetics at University of Edinburgh, who led the study on Viking genes that found individuals with familial ties to two small Scottish communities may be at a higher risk of having a cancer-causing gene.
Wilson hopes to see testing for these genetic abnormalities become more common for these at-risk communities.
“The Ashkenazi Jewish community have BRCA1 and BRCA2 variants that also have a frequency of about one in 40,” he told the BBC. “The Ashkenazi Jewish population in England are able to take part in genetic testing for these genes but that’s not yet the case in Scotland.”
The findings of the most recent University of Edinburgh genetic study are very new. Future developments and offerings from the NHS may be influenced by the results.
Deeper understanding about the genetic make-up of certain population subgroups could lead to new genetic personalized medicine and preventative testing for those at risk of hereditary cancer. In turn, it could also encourage individuals to seek preventative care earlier. Thus, pathologists and clinical laboratory managers should keep an eye on these developments and be prepared to work with geneticists who may develop new screening methods for BRCA1 and BRCA2.
Underfunding of clinical laboratories has led to similar worker walkouts in multiple Australasian nations
Once again, cuts in government spending on pathology services has forced healthcare workers to walk off the job in Australia. This is in line with other pathology doctor and clinical laboratory workers strikes in New Zealand and other Australasian nations over the past few years.
Announcement of a planned closure of the pathology laboratory at 30-bed Cootamundra Hospital in Australia to make room for expanding the emergency department spurred the health worker walkouts.
“Health staff from Cootamundra Hospital, alongside pathology workers from Deniliquin, Tumut, Griffith, Wagga Wagga, and Young will rally in front of their respective facilities” to draw attention to the effect closing the lab would have on critical healthcare services across those areas, Region Riverina reported.
The strikes are drawing attention to unfair pay and poor working conditions that underfunding has brought to the state-run healthcare systems in those nations. They also highlight how clinical laboratories worldwide are similarly struggling with facility closings, unfair pay, and unachievable workloads.
“The proposed closure of Cootamundra’s pathology lab is a short-sighted decision that will have far-reaching consequences for patient care in the region,” NSW Health Services Union (HSU) Secretary Gerard Hayes (above) told Region Riverina. Similar arguments have been made for years concerning the underfunding, pay disparities, and poor working conditions in New Zealand’s government-run clinical laboratories and pathology practices that has led to worker strikes there as well. (Photo copyright: HSU.)
Australia Pathology Lab Closure Stokes Fears
Cootamundra Hospital’s strike was spurred by a planned closure of its pathology laboratory. In May, employees learned of the plans to close the lab as well as surgery and birthing centers to accommodate expansion of the emergency department, Region Riverina reported.
“Pathology workers are already in short supply and this move could see us lose highly skilled professionals from the NSW Health system altogether,” New South Wales (NSW) Health Services Union (HSU) Secretary Gerard Hayes told Region Riverina.
The cuts would not only be detrimental to the area, it would significantly affect patient care, he added.
“This lab is not just profitable; it’s a vital lifeline for Cootamundra Hospital’s [surgical] theater lists and maternity unit,” he said. “Without this lab, patients will face significantly longer wait times for life-saving diagnostic information. This delay could severely impact our ability to provide timely care, especially in emergencies.”
Echoing those sentiments, HSU Union Official Sam Oram told Region Riverina that closing the Cootamundra Hospital lab would put pressure on labs in Wagga and Young and would continue a trend of closing smaller pathology labs. Oram, who organizes for members in Canberra and Murrumbidgee Local Health District, noted that smaller labs in Tumut and Deniliquin could be in danger as well.
“Why should people living in rural and regional areas have fewer and inferior services to Australians living in metropolitan areas?” Michael McCormack, MP, Federal Member for Riverina and former deputy prime minister of Australia, asked Parliament in June, Region Riverinareported. “There’s no right or proper answer to that question. They simply should not,” he added.
Tasmania’s Troubles
Medical scientists recently walked off the job at Launceston General Hospital in Tasmania, Australia, to protest “the government’s ‘inaction’ on recruiting more staff,” according to Pulse Tasmania. The hospital’s lab has a staff shortage of 17 employees, requiring the remaining staff members to handle a much increased workload, Ryan Taylor, a medical laboratory scientist with the Tasmanian Department of Health, told Pulse Tasmania.
“This shortfall is leading to significant and unacceptable challenges … which are causing the Tasmanian community from receiving vital test results that are essential for their health,” Lucas Digney, Industrial Champion, Health and Community Services Union (HACSU) leader, told Pulse Tasmania.
New Zealand Struggles with Its Healthcare Workers
Aotearoa, as New Zealand is known by its indigenous Polynesian population, also struggles with health worker walkouts.
“Medical labs are an essential organ of the health system. Many were stupidly privatized years ago, others still operate within Te Whatu Ora [aka Health New Zealand, the publicly funded healthcare system] with all the resource shortages and stress that go with that,” Newsroom said of the country’s plight in 2023. “There was a view that competition in medical labs would produce greater efficiency, but it has actually produced a mess.”
Dark Daily has covered the ongoing strife in New Zealand’s clinical laboratories over many years. Previous ebriefs highlighted how the strikes were causing delays in critical clinical laboratory blood testing and surgical procedures.
Underfunding in clinical laboratories continues to cause work stoppages in the Australasian countries. But as Dark Daily readers know, it is a growing problem among European nations and in the United States as well.
