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Clinical Laboratories and Pathology Groups

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BMJ Oncology Study Shows 79% Increase in Cancer among People under 50 Years of Age

Findings suggest new medical guidelines may be needed to determine when to perform clinical laboratory cancer screenings on people under 50

From 1990-2019, new diagnoses of early-onset cancer in individuals under 50 years of age increased by 79%, according to a British Medical Journal (BMJ) news release describing research published last year in BMJ Oncology. The question for anatomic pathology laboratories to consider is, why are more people under 50 being diagnosed with cancer than in earlier years? And do medical guidelines need to be changed to allow more cancer screening for individuals under 50-years old?

This new revelation challenges previously held beliefs about the number of younger adults under 50 experiencing early-onset cancer. Patients can sometimes miss symptoms by attributing them to a more benign condition.

“While cancer tends to be more common in older people, the evidence suggests that cases among the under 50s have been rising in many parts of the world since the 1990s. But most of these studies have focused on regional and national differences; and few have looked at the issue from a global perspective or the risk factors for younger adults, say the researchers. In a bid to plug these knowledge gaps, they drew on data from the Global Burden of Disease 2019 Study for 29 cancers in 204 countries and regions,” the BMJ news release states.

According to the news release, “Breast cancer accounted for the highest number of ‘early-onset’ cases in this age group in 2019. But cancers of the windpipe (nasopharynx) and prostate have risen the fastest since 1990, the analysis reveals. Cancers exacting the heaviest death toll and compromising health the most among younger adults in 2019 were those of the breast, windpipe, lung, bowel, and stomach.”

Although these statistics are being seen worldwide, the highest rates are in North America, Australasia, and Western Europe. However, high death rates due to cancer are also being seen in Eastern Europe, Central Asia, and Oceania. Economic disparities in the latter geographical regions may account for both fewer diagnoses and higher death rates.

“And in low to middle income countries, early onset cancer had a much greater impact on women than on men, in terms of both deaths and subsequent poor health,” the BMJ news release noted.

In an editorial they published in BMJ Oncology on the study findings, Ashleigh Hamilton, PhD (left), Academic Clinical Lecturer, and Helen Coleman, PhD (right), Professor, School of Medicine, Dentistry and Biomedical Sciences, both at the Center for Public Health at Queen’s University Belfast in the UK wrote, “The epidemiological landscape of cancer incidence is changing. … Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.” Anatomic pathology laboratories will play an important role in diagnosing and treating younger cancer patients. (Photo copyrights: Queen’s University Belfast.)

What Caused the Increase?

“It’s such an important question, and it points to the need for more research in all kinds of domains—in population science, behavioral health, public health, and basic science as well,” said medical oncologist Veda Giri, MD, Professor of Internal Medicine, Yale School of Medicine, in a news release. Giri directs the Yale Cancer Center Early-Onset Cancer Program at Smilow Cancer Hospital.

Although experts are still trying to determine exactly where these cases are coming from, signs point to both genetic and lifestyle factors, the BMJ news releases noted. Tobacco and alcohol use, diets high in cholesterol and sodium, and physical inactivity are all lifestyle risk factors. Experts recommend a healthy diet and exercise routine with minimal alcohol consumption.

As for family history? “We’re beginning to recognize that family history is very important,” says Jeremy Kortmansky, MD, also a Yale Medicine medical oncologist.

According to CNN Health, these rates of early-onset cancer are more common in female patients, with rates going up an average of 0.67% each year.

“For young women who have a significant family history of cancer in the family, we are starting to refer them to a high-risk clinic—even if the cancer in their family is not breast cancer,” Kortmansky noted.

Doctors advise patients to implement healthy habits into their lives, not ignore symptoms, advocate for themselves, and be aware of their family history. Cancer patients may be prescribed cancer treatments at a much earlier age. Medical guidelines for patients may continue to shift and change. And oncologists may be incorporating alternative therapies to help younger patients deal with the shock of their diagnosis.

Will Cancer Rates Continue to Rise?

“Based on the observed trends for the past three decades, the researchers estimate that the global number of new early-onset cancer cases and associated deaths will rise by a further 31% and 21% respectively in 2030, with those in their 40s the most at risk,” the BMJ news release noted.

In an editorial they penned for BMJ Oncology on the findings of the cancer study titled, “Shifting Tides: The Rising Tide of Early-Onset Cancers Demands Attention,” Ashleigh Hamilton, PhD, Academic Clinical Lecturer, and Helen Coleman, PhD, Professor, School of Medicine, Dentistry and Biomedical Sciences, both at the Center for Public Health at Queen’s University Belfast in the UK wrote, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored. It is crucial that we better understand the underlying reasons for the increase in early-onset cancers, in order to inform prevention strategies.”

Clinical laboratories should be aware of these findings and the changing landscape of cancer screenings, as they will play a key role in diagnoses. Younger patients may be advocating for cancer screenings and doctors may be ordering them depending on the patient’s symptoms and family history. Anatomic pathology professionals should expect new guidelines when it comes to cancer diagnostics and treatment.

—Ashley Croce

Related Information:

Global Surge in Cancers among the Under 50s over Past Three Decades

Shifting Tides: The Rising Tide of Early-Onset Cancers Demands Attention

Global Trends in Incidence, Death, Burden and Risk Factors of Early-Onset Cancer from 1990 to 2019

Cancer Diagnosis Rates are Going up in Younger Adults, Study Finds, Driven Largely By Rises in Women and People in Their 30s

Early Onset Cancer Cases Rise 80% in Past Three Decades, BMJ Survey Finds

Cancer in Younger People Is on the Rise: Knowing Your Family History Can Help

Study Points to Big Surge in Under-50 Cancer Cases

Researchers See Surge in Number of People under 50 Diagnosed with Cancer

Dutch Researchers Investigating Prostate Cancer Discover That a Common Protein Increases Resistance to Therapy in Aggressive Cancer Cells

Study may lead to clinical laboratory involvement in repurposing hormonal treatments to prevent cancer treatment resistance

Diagnosing prostate cancer and identifying which patients have aggressive forms of the cancer has been a challenge. But new insights into how aggressive cancers become resistant to drug therapies—and the discovery of a way to repurpose hormonal treatment to block or slow aggressive prostate cancer—may lead to clinical laboratories monitoring the progress of patients’ being treated with this new type of therapy.

Instead of treating tumors directly, the new approach developed by an international team of scientists would target proteins that typically regulate a cell’s circadian rhythm, but which have been found to be helping cancerous cells become resistant to treatment therapies.

That’s according to a news release from the Antoni van Leeuwenhoek Netherlands Cancer Institute (NKI), Amsterdam, and Oncode Institute, Utrecht, in the Netherlands. The NKI is an oncology-focused hospital and research institute, and Oncode is an independent organization specializing in molecular oncology.

The researchers published their findings in Cancer Discovery, a journal of the American Association for Cancer Research (AACR), titled, “Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence.”

Wilbert Zwart, PhD

“Our discovery has shown us that we will need to start thinking outside the box when it comes to new drugs to treat prostate cancer and test medicines that affect the circadian clock proteins in order to increase sensitivity to hormonal therapy in prostate cancer,” said Wilbert Zwart, PhD (above), Lead Researcher and Senior Group Leader Oncogenomics Division at NKI, in a news release. This discovery could give clinical laboratories and anatomic pathology groups an effective way to monitor new forms of cancer hormonal treatments. (Photo copyright: Netherlands Cancer Institute.)

Breakthrough Could Mean New Treatment for Aggressive Cancer

The aim of prostate cancer hormone therapy (AKA, androgen suppression therapy) is to halt signals by male hormones (usually testosterone) that stimulate tumor growth. This approach works until cancer becomes resistant to the drug therapy.

So, the challenge in metastatic prostate cancer treatment is finding a drug that prevents resistance to hormonal therapy.

In addressing the challenge, the researchers made a surprising discovery about what exactly dilutes anti-hormonal therapy’s effectiveness. Proteins that regulate the body’s sleep-wake cycle, or circadian rhythm, were found to also “dampen the effects of the anti-hormonal therapy,” according to the study.

“Prostate cancer cells no longer have a circadian rhythm. But these ‘circadian clock’ proteins acquire an entirely new function in the tumor cells upon hormonal therapy: they keep these cancer cells alive, despite treatment. This has never been seen before,” said Wilbert Zwart, PhD, Lead Researcher and Senior Group Leader Oncogenomics Division, NKI, in the news release.

The research suggests treatment for metastatic prostate cancer requires drugs “which influence the day-and-night rhythm of a cell,” and not necessarily medications that fight cancer, Technology Networks noted.

“Fortunately, there are already several therapies that affect circadian proteins, and those can be combined with anti-hormonal therapies. This lead, which allows for a form of drug repurposing, could save a decade of research,” Zwart added.

Questioning Hormonal Therapy Resistance

In their paper, the Dutch researchers acknowledged that androgen receptor (AR)-targeting agents are effective in prostate disease stages. What they wanted to learn was how tumor cells bypass AR suppression.

For the study, the scientists enrolled 56 patients with high-risk prostate cancer in a neoadjuvant clinical trial. Unlike adjuvant therapy, which works to lower the risk that cancer will return following treatment, the purpose of neoadjuvant therapy is to reduce the size of a tumor prior to surgery or radiation therapy, according to the National Institute of Health (NIH) National Cancer Institute (NCI).

The researchers performed DNA analysis of tissue samples from patients who had three months of anti-hormonal therapy before surgery. They observed that “genes keeping tumor cells alive were controlled by a protein that normally regulates the circadian (body) clock,” said Simon Linder, PhD student and researcher at NKI, in the news release.

“We performed integrative multi-omics analyses on tissues isolated before and after three months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state,” the researchers wrote in Cancer Discovery.

“Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward pro-survival signaling and uncovered the circadian regulator ARNTL [Aryl hydrocarbon receptor nuclear translocator-like protein 1] as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development,” the scientists concluded.

More Research Planned

The scientists expressed intent to follow-up with Oncode to develop a drug therapy that would increase anti-hormonal therapy’s effectiveness in prostate cancer patients.

Given the molecular processes involved in the researchers’ discovery, there may be a supportive role for clinical laboratories and anatomic pathology groups in the future. But that can only happen after more studies and a US Food and Drug Administration (FDA) review of any potential new therapy to combat hormonal treatment resistance in prostate cancer patients.

Donna Marie Pocius

Related Information:

Drug-induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer Towards Androgen-Independence

Prostate Cancer Hijacks Tumor Cells Biorhythm to Evade Hormone Therapy

Scientists Make a Prostate Cancer Breakthrough

Prostate-specific Antigen Test Fact Sheet

Types of Hormone Therapy