Tag: cancer screening

Categories : CancerTags :

New Metastatic Breast Cancer Treatments have Aided Mortality Decline

On By ModernMedia
Photo by National Cancer Institute on Unsplash

Deaths from breast cancer dropped 58% between 1975 and 2019 due to a combination of screening mammography and improvements in treatment, according to a new study led by Stanford Medicine clinicians and biomedical data scientists.

Nearly one-third of the decrease (29%) is due to advances in treating metastatic breast cancer, also known as stage 4 breast cancer or recurrent cancer. Although these advanced cancers are not considered curable, women with metastatic disease are living longer than ever.

The analysis helps cancer researchers assess where to focus future efforts and resources.

“We’ve known that deaths from breast cancer have been decreasing over the past several decades, but it’s been difficult or impossible to quantify which of our interventions have been most successful, and to what extent,” said Jennifer Caswell-Jin, MD, assistant professor of medicine. “This type of study allows us to see which of our efforts are having the most impact and where we still need to improve.”

Caswell-Jin and Liyang Sun are co-first authors of the study, which was published in the Journal of the American Medical Association. Sylvia Plevritis, PhD, professor and chair of biomedical data science, and Allison Kurian, MD, MSc, professor of medicine and of epidemiology and population health, are co-senior authors.

The study was a collaborative effort by a national consortium of researchers called CISNET, or the Cancer Intervention and Surveillance Modeling Network. CISNET was established in 2000 by the National Cancer Institute to understand the impact of cancer surveillance, screening and treatment on incidence and mortality. Doing so requires sophisticated computer algorithms capable of modelling the natural course of the disease and the typical treatment paths of individual patients, then translating that information to population-level data collected by the national Surveillance, Epidemiology, and End Results Program, or SEER registry, from 1975 to 2019.

The study is the third in a trio of papers from CISNET published since 2005 that assess the relative contributions of regular screening and treatment advances on breast cancer deaths. The previous two papers informed national guidelines and helped cancer researchers focus their efforts on the most intractable problems.

“Twenty years ago, there was a question whether routine screening mammography actually decreased the number of deaths from breast cancer,” Plevritis said. But in 2005, she and other CISNET researchers published a paper in the New England Journal of Medicine that conclusively demonstrated that screening was responsible for anywhere from 28% to 65% (different models came up with varying degrees of impact) of the reduction in mortality by 2000 between 1975 and 2000.

The second paper, published in 2018 in the Journal of the American Medical Association, highlighted the differences in treatment responsiveness and survival outcomes among women with differing breast cancer subtypes from 2000 to 2012, pinpointing subgroups with poorer survival.

“We found that, while screening still had an important impact, most of the decline in annual deaths was due to improvements in treating early-stage breast cancer based on each cancer’s molecular profile,” Plevritis said.

The current study is the first to explicitly include patients with metastatic breast cancer in its models. The finding that 29% of the decrease in mortality is due to advances in treating metastatic breast cancer both surprised and gratified the researchers.

“Initially, we assumed that treatment of advanced disease was unlikely to make a significant contribution to the declines in mortality we documented in the previous two papers,” Caswell-Jin said. “But our treatments have improved, and it’s clear that they are having a significant impact on annual mortality.”

The CISNET researchers used four computer models to assess the SEER data from 1975 to 2019 — one developed at Stanford Medicine in the Plevritis Lab, one by researchers at the Dana-Farber Cancer Institute, one at MD Anderson Cancer Center, and another jointly developed by researchers at the University of Wisconsin and Harvard Medical School. The four models came up with remarkably similar estimates for the impact of each intervention: screening mammography, treatment of early-stage (stages 1, 2 or 3) breast cancer and treatment of metastatic breast cancer.

The models reproduced the decline in mortality in breast cancer known from SEER data, from 48 per 100 000 women dying of breast cancer each year in 1975 to 27 per 100,000 in 2019, a decrease of about 44%. The models arrived at a larger estimated reduction in mortality of about 58% because the incidence of breast cancer has risen during the same period and more women would have died had screening and treatments not improved.

The models concluded that about 47% of this reduction in mortality is the result of improved treatments for early-stage breast cancer, and about 25% is attributed to screening mammography. The remainder, or about 29%, is due to improvements in treating metastatic disease.

“Designing the new model, which had to account for individuals with non-metastatic cancer who underwent treatment but later progressed to metastatic cancer, and who may have been treated with multiple drugs over the course of their disease, was extremely complex,” Plevritis said. “It took about four years. But it was really satisfying when we were able to validate the model’s behaviour and see that all four models from different institutions, which used the new model inputs in different ways, delivered consistent findings. The models not only make sense, but also produce meaningful insights.”

The impact of treating metastatic disease is exemplified by the increases in median survival time after metastasis: Patients diagnosed in 2000 with metastatic disease lived an average of 1.9 years versus an average of 3.2 years for those diagnosed in 2019. Survival time varies by subgroup status, however. Patients with what are known as oestrogen receptor-positive and HER2 positive cancers saw an average increase in survival time of 2.5 years. Those with oestrogen receptor-positive and HER2-negative cancers lived an average of 1.6 years longer, but those with cancers that are oestrogen receptor-negative and HER2-negative lived about 0.5 years longer in 2019 than in 2000.

“It was meaningful as a breast oncologist to spend time with this history and see real progress over the past decades,” Caswell-Jin said. “There is much more work to be done; metastatic breast cancer isn’t yet curable. But it is rewarding to see that advances have made a difference in these numbers,” she added. “Our scientific and clinical work is helping our patients live longer, and I believe deaths from breast cancer will continue to steadily decline as innovation continues to grow.”

Source: Stanford Medicine

Categories : Cancer Cardiovascular DiseaseTags :

Exercise Stress Tests Pick up More than Just Cardiovascular Problems

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Photo by Stephen Andrews

The exercise stress test, which involves treadmill exercise test with electrocardiogram (ECG), is one of the most familiar tests in medicine. While exercise testing typically is focused on diagnosing coronary artery disease, a recent study from Mayo Clinic finds that exercise test abnormalities, such as low functional aerobic capacity, predicted non-cardiovascular causes of death such as cancer in addition to cardiovascular-related deaths. These new findings are published in Mayo Clinic Proceedings.

The exercise stress test is noninvasive, easily available and provides important diagnostic information. In addition to the ECG itself, the test produces data on functional aerobic capacity, heart rate recovery and chronotropic index, the standardised measure of heart rate during exercise that reflects age, resting heart rate and fitness.

“In our exercise testing cohort, non-cardiovascular deaths were more frequently observed than cardiovascular deaths,” says Thomas Allison, PhD, MPH, director of Mayo Clinic’s Integrated Stress Testing Center and the study’s senior author. “Though this was a cardiac stress test, we found that cancer was the leading cause of death, at 38%, whereas only 19% of deaths were cardiovascular. Exercise test results including low exercise capacity, low peak heart rate, and a slow recovery of the heart rate after exercise test were associated with increased mortality.”

The study looked at 13 382 patients who had no baseline cardiovascular issues or other serious diseases and who had completed exercise tests at Mayo Clinic between 1993 and 2010, then were followed closely for a median period of 12.7 years.

The findings suggest that clinicians should focus not only on ECG results but on data in the exercise test results such as low functional aerobic capacity, low chronotropic index and abnormal heart rate recovery. Patients should be encouraged to increase their physical activity if these results are atypical, even if the ECG results show no significant cardiovascular-related risk, Dr Allison says.

Source: Mayo Clinic

Categories : CancerTags :

How Accurate is Supplemental Ultrasound in Breast Cancer Screening Failures?

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Photo by National Cancer Institute on Unsplash

Dense breast tissue, which contains a higher proportion of fibrous tissue than fat, is a risk factor for breast cancer and also makes it more difficult to identify cancer on a mammogram. Many US states have enacted laws that require women with dense breasts to be notified after a mammogram, so that they can choose to undergo supplemental ultrasound screening to improve cancer detection. A recent study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society, evaluated the results of such additional screening to determine its benefits and harms to patients.

Although supplemental ultrasound screening may detect breast cancers missed by mammography, it requires additional imaging and may lead to unnecessary breast biopsies among women who do not have breast cancer. Therefore, it is important to use supplemental ultrasound only in women at high risk of mammography screening failure – in other words, women who develop breast cancer after a mammogram shows no signs of malignancy.

Brian Sprague, PhD, of the University of Vermont Cancer Center, and his colleagues evaluated 38 166 supplemental ultrasounds and 825 360 screening mammograms without supplemental ultrasounds during 2014–2020 at 32 US imaging facilities within three regional registries of the Breast Cancer Surveillance Consortium.

The team found that 95.3% of supplemental ultrasounds were performed in women with dense breasts. In comparison, 41.8% of mammograms without additional screening were performed in women with dense breasts.

Among women with dense breasts, a high risk of interval invasive breast cancer was present in 23.7% of women who underwent ultrasounds, compared with 18.5% of women who had mammograms without additional imaging.

The findings indicate that ultrasound screening was highly targeted to women with dense breasts, but only a modest proportion of these women were at high risk of mammography screening failure. A similar proportion of women who received only mammograms were at high risk of mammography screening failure.

“Among women with dense breasts, there was very little targeting of ultrasound screening to women who were at the highest risk of a mammography screening failure. Rather, women with dense breasts undergoing ultrasound screening had similar risk profiles to women undergoing mammography screening alone,” said Dr Sprague. “In other words, many women at low risk of breast cancer despite having dense breasts underwent ultrasound screening, while many other women at high risk of breast cancer underwent mammography alone with no supplemental screening.”

Clinicians can consider other breast cancer risk factors beyond breast density to identify women who may be appropriate for supplemental ultrasound screening. Publicly available risk calculators from the Breast Cancer Surveillance Consortium are available that also consider age, family history, and other factors (https://www.bcsc-research.org/tools).

Source: Wiley

Categories : CancerTags :

Digital Rectal Exam is not Useful in Detecting Prostate Cancers Early

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Healthcare worker pulling on gloves
Image by Gustavo Fring on Pexels

A common method of detecting prostate cancer may not be accurate enough as a reliable screening tool by itself, scientists in Germany have warned. The digital rectal exam (DRE) is widely used by medical professionals to check the prostate gland with a finger for unusual swelling or lumps in the rectum as an initial check for the signs of prostate cancer in men.

But new research by scientists of the PROBASE trial coordinated at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, suggests the technique may be missing many cancers in their early stages.

The findings, presented at the European Association of Urology Annual Congress in Milan, could have implications for the early detection of prostate cancer, say the researchers. They are calling for other testing methods to be used in routine screening instead.

“One of the main reasons for screening for prostate cancer is to detect it in patients as early as possible as this can lead to better outcomes from treatment,” said Dr Agne Krilaviciute, a researcher at DKFZ and lead author of the study. “But our study suggests that the DRE is simply not sensitive enough to detect those early stage cancers.”

The PROBASE trial is a multicentre German prostate cancer screening study involving 46 495 men aged 45 years who were enrolled between 2014 and 2019. The men have since been had follow ups to assess their health in the years after the screening. Half of the participants in the trial were offered prostate specific antigen (PSA) blood test immediately at age 45 while the other half were initially offered DRE with delayed PSA screening at age 50.

Ultimately, 6537 men in the delayed screening group underwent DRE and only 57 of these men were referred for a follow-up biopsy due to suspicious findings. Only three were found to have cancer.

When compared to the detection rate using other methods, such as a PSA test, the rate of detection using DRE was substantially lower, says Dr Krilaviciute.

“The DRE was giving a negative result in 99% of cases and even those that were deemed to be suspicious had a low detection rate,” says Dr Krilaviciute. “Results we’ve seen from the PROBASE trial show that PSA testing at the age of 45 detected four times more prostate cancers.”

The researchers believe one of the reasons why the DRE might be failing to detect cancers, particularly in younger men, is because the changes in the tissue in the prostate may be too slight to detect with a finger. In addition, some cancers occur in a part of the prostate that cannot be easily reached by a finger.

“Early stage cancer may not have the size and stiffness to be palpable,” said Professor Peter Albers, a urologist at Düsseldorf University who was the senior author of the study.

“Separate analysis that used MRI scans before biopsies to locate cancers in the prostate showed that about 80% of these are in an area that should be easy to reach with a finger and still cancers were not detectable by DRE.”

The researchers are now calling for widespread use of PSA testing and MRI scans as part of screening programmes instead of DRE.

“If the aim of a screening programme is to pick up cancers as early as possible and the current screening tool isn’t doing that job, then that is a fundamental failure of that approach,” said Professor Albers. “We speculate in our paper that not only is the DRE not useful for detecting cancer, but it may also be one reason why people don’t come to screening visits – the examination probably puts a lot of men off.

“In Germany, for example, the participation rate is less than 20% in the screening programme for men 45 to 50 years. If we were to offer PSA testing instead, more of them might be willing to come.”

Source: European Association of Urology

Categories : CancerTags :

Defensiveness Keeping People from Taking at-home Colorectal Cancer Stool Tests

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Photo by Priscilla du Preez on Unsplash

Despite colorectal cancer being highly treatable, especially when detected early, many people do not undergo recommended screening, even with the availability of at-home stool faecal immunochemical test (FIT) kits. New research published in CANCER reveals that people who react defensively to the invitation to get screened are less likely to take part.

For the study, Nicholas Clarke, PhD, of Dublin City University in Ireland, surveyed individuals in Dublin who had been invited to participate in a FIT screening program in 2008–2012. Questionnaires were mailed in September 2015 to all individuals who were invited to participate (over two screening rounds) but had declined and a random sample of individuals who had participated. Following two reminders, questionnaires were completed by 1988 people who participated in screening and 311 who did not.

Those who did not do FIT-based screening were more likely to provide responses indicating greater defensiveness. This was apparent for all questions related to the different domains of what is called defensive information processing (DIP). The four domains of DIP include:

  • attention avoidance (reducing risk awareness by avoidance),
  • blunting (active mental disengagement through avoidance and accepted denial),
  • suppression (acknowledging others’ risk but avoiding personal inferences through self-exemption beliefs), and
  • counter-argumentation (arguing against the evidence).

“People who react defensively to the invitation to colorectal cancer screening are less likely to take part, and this seems to be due to such misconceptions that having a healthy lifestyle or having regular bowel movements means that they do not need to be screened. Similarly, some people believe testing can be delayed while they wait for a ‘better’ test (even though the current test works very well) or wait until their other health concerns are under control,” explained Dr Clarke. “Some people also react defensively because they believe cancer is always fatal, which is not true. All of these factors can result in people making a decision not to take the home-based screening test.”

Dr Clarke noted that the study’s findings indicate that even well-designed health communication campaigns and proactive screening programs may be hindered by individuals’ defensive beliefs. “The measures used in this study could be used to help identify people who may need extra support to take part in colorectal cancer screening programs worldwide,” he said. “The results suggest that screening programs need strategies to decrease procrastination and address misconceptions about colorectal cancer and screening.”

He also stressed the importance of trying to make colorectal cancer screening something that everyone routinely does when they reach middle age.

An accompanying editorial by Beverly Beth Green MD, MPH advocates for additional research to test different strategies, such as financial incentives, for decreasing DIP in participants.

Source: Wiley

Categories : CancerTags :

A New Analytical Technique for Dense Breast Tissue Mammograms

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Source: National Cancer Institute

Researchers have developed a two-pronged approach to imaging breast density in mice, resulted in better detection of changes in breast tissue, including spotting early signs of cancer. If applied in humans, the technology may also help with prognosis of disease as density can be linked to specific patterns of mammary gland growth, including signs of cancer development. The findings appeared in the American Journal of Pathology.

“Having a means to accurately assess mammary gland density in mice, just as is done clinically for women using mammograms, is an important research advance,” said Priscilla A. Furth, MD, professor of oncology and medicine at Georgetown Lombardi Comprehensive Cancer Center, and corresponding author of the study. “This method has the benefit of being applicable across all ages of mice and mammary gland shapes, unlike some methods used in earlier studies.”

While working as an undergraduate in Furth’s lab, Brendan Rooney developed an innovative analytic computer program (C’20), which allowed for sorting of mammary gland tissue to one of two imaging assessments. At first, Rooney looked at younger mouse glands and found that a program that removed background ‘noise’ in those images helped boost detection of abnormalities in what are typically rounder, more lobular tissues. But as aging occurs and the chances of developing cancer increase, lobules diminish and ridges become more apparent, just as falling autumn leaves expose tree branches. The mammary ridges represent ducts that carry milk and other fluids. When the de-noising technique was applied to the images from the older mice, it was found to be less reliable in detecting ridges. Therefore Rooney and the team turned to a different imaging program, which has primarily been used to detect blood vessel changes in the eye’s retina.

“The idea for the analytic program came from routine visual observations of tissue samples and the challenges inherent in observing differences in breast tissue with just a microscope. We found that visual human observations are important but having another read on abnormalities from optimal imaging programs added validity and rigor to our assessments,” says Rooney, the lead author of the study. “Not only does our program result in a high degree of diagnostic accuracy, it is freely available and easy to use.”

Now that the broad strokes of the research have been laid down and proof-of-principle has been established, Rooney has started medical school with a possible eye toward specializing in oncology. Both Furth and Rooney believe that future studies will need to refine and streamline their research approach in mice, including better density measurements that could enable sorting of samples into higher and lower probabilities of cancer.

Source: Georgetown University Medical Center

Categories : CancerTags :

New Recommendations for Earlier Breast Cancer MRI Screening

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This screening MRI detected a very small cancer (circled) in the patient’s breast.
Credit: Dr. Kathyrn Lowry

Annual MRI screenings starting at ages 30 to 35 may slash breast-cancer mortality by more than 50% among women with genetic changes in three genes, according to a study published in JAMA Oncology.

The pathogenic variants are in the ATM, CHEK2 and PALB2 genes – which collectively are as prevalent as the much-reported BRCA1/2 gene mutations. The study authors state that their findings support earlier MRI screening in these women.

“Screening guidelines have been difficult to develop for these women because there haven’t been clinical trials to inform when to start and how to screen,” said lead author Dr Kathryn Lowry.

The work was a collaboration of the Cancer Intervention and Surveillance Modeling Network (CISNET), the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium, and the Breast Cancer Surveillance Consortium.

To arrive at their model, the researchers input age-specific risk estimates from CARRIERS involving some 64 000 women and recent published data for screening performance.

“For women with pathogenic variants in these genes, our modeling analysis predicted a lifetime risk of developing breast cancer at 21% to 40%, depending on the variant,” Dr Lowry said. “We project that starting annual MRI screening at age 30 to 35, with annual mammography starting at age 40, will reduce cancer mortality for these populations of women by more than 50%.”

The simulations compared the combined performance of mammography and MRI against mammography alone, and projected that annual MRI conferred significant additional benefit to these populations.

“We also found that starting mammograms earlier than age 40 did not have a meaningful benefit but increased false-positive screens,” Dr Lowry added.

Results from CISNET models have informed past guidelines, including the 2009 and 2016 U.S. Preventive Services Task Force recommendations for breast cancer screening in average-risk women.

“Modelling is a powerful tool to synthesise and extend clinical trial and national cohort data to estimate the benefits and harms of different cancer control strategies at population levels,” said senior author Dr Jeanne Mandelblatt.

The study projected about four false-positive screening results and one to two benign biopsies per woman over a 40-year screening span, the authors noted.

To get any benefit from genetic susceptibility-based screening guidelines, a woman would have to know beforehand that she carries the gene, yet most often a genetic test panel is done after a positive cancer result – too late for any benefit.

“People understand very well the value of testing for variants in BRCA1 and BRCA2, the most common breast cancer predisposition genes. These results show that testing other genes, like ATM, CHEK2, and PALB2, can also lead to improved outcomes,” said senior author Dr Mark Robson.

The researchers hope their analysis will aid the National Comprehensive Cancer Network (NCCN), the American Cancer Society and other organizations that issue guidance for medical oncologists and radiologists.

“Overall what we’re proposing is slightly earlier screening than what the current guidelines suggest for some women with these variants,” said senior author Professor Allison Kurian. “For example, current NCCN guidelines recommend starting at age 30 for women with PALB2, and at 40 for ATM and CHEK2. Our results suggest that starting MRI at age 30 to 35 appears beneficial for women with any of the three variants.”

Source: University of Washington

Categories : CancerTags :

Unemployed People Missed Out on Cancer Screenings

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Source: National Cancer Institute

In a recent study, unemployed individuals in the US were less likely to have health insurance and be up to date on getting recommended cancer screening tests. Analyses published in the journal CANCER revealed that their lack of health insurance coverage completely accounted for their lower screening rates.

During the COVID pandemic, unemployment rates in the United States have risen to levels not seen since the Great Depression. To examine associations between unemployment, health insurance, and cancer screening, Stacey Fedewa, PhD, of the American Cancer Society, and her colleagues analysed information from adults under age 65 years who responded to a nationally representative annual survey of the general population.

Unemployed adults were four times more likely to lack insurance than employed adults (41.4% vs 10.0%). A lower proportion of unemployed adults had received up-to-date cervical (78.5% vs 86.2%), breast (67.8% vs 77.5%), colorectal (41.9% vs 48.5%), and prostate (25.4% vs 36.4%) cancer screening. These differences were eliminated after accounting for health insurance coverage.

“People who were unemployed at the time of the survey were less likely to have a recent cancer screening test and they were also less likely to be up-to-date with their cancer screenings over the long term. This suggests that being unemployed at a single point in time may hinder both recent and potentially longer-term screening practices,” said Dr. Fedewa. This can increase a person’s risk of being diagnosed with late-stage cancer, which is more difficult to treat than cancer that is detected at an early stage.

“Our finding that insurance coverage fully accounted for unemployed adults’ lower cancer screening utilisation is potentially good news, because it’s modifiable,” Dr Fedewa added. “When people are unemployed and have health insurance, they have screening rates that are similar to employed adults.”

The findings highlight insurance coverage’s importance in access to recommended cancer screening tests and indicate that insurance needs to be extended to all people, regardless of their employment status.

Source: Wiley