screening

Breast cancer: 3D mammogram better than 2D scan for screening, study finds

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  • In a large study of more than one million women, researchers compared how well 2D and 3D mammograms detect breast cancer.
  • They found that 3D mammograms were significantly more effective than 2D mammograms.
  • The scans are currently undergoing clinical trials.

Breast cancer is the most common cancer among women in the United States, and the second leading cause of cancer death in women after lung cancer.

According to the American Cancer SocietyTrusted Source, classifications of breast cancer stages include:

  • Localized — cancer has not spread outside of the breast
  • Regional — cancer has spread outside the breast to nearby structures
  • Distant — cancer has spread to distant parts and other organs of the body

The 5-year survival rate for breast cancer when detected early in its localized stage is 99%Trusted Source. The figure drops to 86% when cancer reaches the regional stage, and 30% when in the distant stage. Regular screening for breast cancer can help individuals identify cancer when it is more treatable.

Currently, the standard of care for screening is a two-dimensional (2D) digital mammography. Studies show that mammography can detect around 87%Trusted Source of breast cancers. This means that around 1 in 8 cases may not be detected.

Digital breast tomosynthesisTrusted Source (DBT), also called a 3D mammogram, is a newer screening technology that captures x-ray images from multiple angles allowing radiologists to see 3D images of breast tissue, as opposed to the single image from a standard 2D mammogram.

Research shows that DBT is linked to a 21%Trusted Source increase in cancer detection compared to mammography. It is also shown to have particularly good results for younger womenTrusted Source and those with denseTrusted Source breasts.

Further study of screening methods for breast cancer could increase breast cancer survival rates.

Recently, researchers analyzed healthcare data from the U.S. to determine whether DBT or mammography yielded higher cancer detection rates.

Dr. Debbie Bennett, Associate Professor of Radiology at Washington University’s Siteman Cancer Center, not involved in the study, told Medical News Today:

“This study analyzed screening mammograms, which are done in women without symptoms for early detection of breast cancer. The study found that mammograms with tomosynthesis (3D mammograms) were better than standard digital mammograms at finding breast cancer and avoiding false positives.”

The study was published in Radiology.

Large study of over one million women

For the study, the researchers analyzed healthcare data from 1,100,447 women aged 40 to 79 years old from across the U.S. All women were screened with either DBT or mammography between 2014 and 2020.

In total, 9,714 cancers were detected: 3421 from mammography and 6293 from DBT.

Ultimately, the researchers found DBT had a cancer detection rate of 5.3 per 1000 examinations, whereas mammography had a cancer detection rate of 4.5 per 1000 examinations.

DBT also delivered lower false positive and false negative results than mammograms. These findings remained after adjusting for potential confounders.

Whereas more people underwent biopsy after DBT, around 30% of biopsies from both DBT and mammograms returned positive.

This study also found that DBT works similarly for women with dense and non-dense breasts.

Dense breasts occur when breasts have more glandular and fibrous tissue than fatty breast tissue. This can make mammograms harder to read and reduce their accuracy. For this reason, the FDA now requiresTrusted Source mammogram reports to include breast density information.

2D vs. 3D breast cancer mammography

To understand when mammography or DBT may be preferable, Dr. Jennifer Chen, lead breast imager at City of Hope Orange County Lennar Foundation Cancer Center in Irvine, California, not involved in the study, told MNT:

“DBT generates three-dimensional images of the breast, allowing physicians to see the breast from more angles and in greater detail. 3D imaging is especially recommended for women with dense breasts because traditional two-dimensional often cannot produce a clear image when high-density tissue is present.”

Dr. Bennett noted that while DBT is generally preferable to standard mammography, the reverse may be true in rare situations, such as when women are unable to hold still for DBT.

MNT also spoke with Dr. Liane Philpotts, FACR, professor of Radiology and Biomedical Imaging at Yale School of Medicine, Section Chief of the Breast Imaging Eastern Region at Smilow Cancer Hospital and co-author of Breast Tomosynthesis, not involved in the study.

Dr. Philpotts said:

“For patients with predominantly fatty breasts (density A), 2D mammography will usually suffice. As soon as there is some fibro glandular breast density, DBT ’sees’ through the tissue better, resulting in more cancers detected and fewer [incorrect results]. Also, for women with dense breasts, having supplemental screening- via ultrasound or MRI, for example- has been shown that the advantages of DBT may not be as great.”

Study limitations 

When asked about the limitations of the findings, Dr. Chen told MNT:

“A limitation of the study is that it is retrospective and observational. The researchers used data from women screened with 2D during an earlier period and compared it to those screened with 3D more recently, which means there is not an absolute comparison of the same cohort.”

“Additionally, because the 2D data lacked important patient characteristics, including breast density, race, and screening intervals, the population study group was not randomized, and there may have been selection bias. Also, the characteristics of detected cancers were not evaluated, and long-term outcomes for the 3D patients were not studied. Further research on the long-term benefits of 3D is important.” she added.

Implications for breast cancer screening

Dr. Philpotts told MNT that while DBT is preferable for most women, those with non-dense breasts may be better served by 2D mammograms alone as these require slightly less radiation.

Dr. Bennett added: “Although tomosynthesis mammograms seem preferable to standard mammography for most women, it is too early to say whether standard of care for breast cancer detection should change. A large trial is underway which randomly assigns women to either type of mammogram screening. Results from that trial should address the limitations described above and provide important information on whether the standard of care for breast cancer screening should change.”

MNT also spoke with Dr. Paul Friedman, Section Chief of Breast Imaging, Attending Radiologist, and Medical Director of the Rippel Breast Center, who was not involved in the study. Dr. Friedman told MNT:

“It’s important for patients to know their risk factors for breast cancer- especially family and genetic history. Many genetic cancers can present early and be aggressive. Patients should use calculation tools provided by breast centers or online to calculate their risks. However, they should also be aware that even if they don’t have elevated risk they are still at risk for breast cancer with the general population which is significant- 1 in 8 women.”

“I would also remind patients that breast cancer detection is becoming an individualized experience and each patient in conjunction with their personal physician and radiologist may benefit from adjunct screening tools- such as ultrasound screening and Breast MRI. Not every test is the best test for every patient and it’s important to have your care tailored to what works best for you and what helps the radiologist evaluate your breast tissue the best,” he concluded.

Critical shortcoming of NordICC trial is in interpretation of ‘screening’

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“Should you still get a colonoscopy?” “A landmark study…found only meager benefits for the group of people invited to get the procedure.” “Doctors push back against European study that casts doubt.”

These are just some of the media reports surrounding the Nordic-European Initiative on Colorectal Cancer (NordICC) Study Group paper, “Effect of colonoscopy screening on risks of colorectal cancer and related death,” published in The New England Journal of Medicine in October.

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Having witnessed the recent explosion of medical misinformation, especially during the COVID-19 pandemic, I initially wondered why this study would be circulated by one of the most respected medical journals in the world. After reading the study design in more detail, I realized that the critical shortcoming of the study is the terminology employed by the authors; specifically, the interpretation of the word “screening.”

Screening saves lives

As a gastroenterologist with a primary focus in colorectal cancer screening and prevention, I recognize that colorectal cancer is the second leading cause of cancer death among American men and women combined. Colorectal cancer affects more than 150,000 Americans every year, with 52,580 expected deaths in 2022 alone. It is estimated that 60% of these deaths could be prevented with screening.

The good news is that colorectal cancer screening rates in the U.S. have steadily increased since the 1980s, with a subsequent decrease in colorectal cancer incidence. As of 2020, 71.6% of adults aged 50 to 75 years reported being up to date with colorectal cancer screening using various modalities. However, the lifetime risk for developing colorectal cancer for an average-risk American is still one in 24. In comparison, the lifetime risk of dying in a car crash is estimated to be one in 107.

Invitation does not equal screening

The NordICC trial is a randomized controlled trial involving healthy men and women aged 55 to 64 years from population registries in Poland, Norway, Sweden and the Netherlands between 2009 and 2014. Researchers randomly assigned individuals in a 1:2 ratio to receive an invitation to undergo a colonoscopy or to receive no invitation. The invitation consisted of a letter with the appointment date and time for a prescheduled colonoscopy, educational pamphlets, and contact information. This letter was mailed about 6 weeks before the scheduled date. No other colorectal cancer screening tests were offered.

Colonoscopy was performed in 42% of the invited group, with a 50% decrease in colorectal cancer-associated death. The study estimated a 31% decrease in colorectal cancer incidence if all study participants had undergone colonoscopy. However, the risk for death from any cause in the invited group (11.03%) and the usual care group (11.04%) showed no significant difference.

The results of this study clearly show that screening colonoscopy reduces colorectal cancer — when it is performed. This translates to decreased cancer treatment and surveillance costs, as well as a diminished emotional burden. In the U.S., the conversation about completing a colorectal cancer screening test may occur over the course of several clinic visits, as patients are often hesitant to discuss “a scope going up there.” If a patient refuses screening, this decision is documented in their medical record and can be reassessed at a future appointment. Mailing a letter with an assigned procedure date and time overlooks an opportunity for patients to participate in the decision-making process. As evidenced by the study’s colonoscopy completion rate, most invitation letters likely ended up in the trash; 58% of the invited study group did not undergo screening.

In actuality, the NordICC trial assessed the response to mailed invitation, rather than the effectiveness of screening colonoscopy. Regrettably, the title wording invites misinterpretation because “screening” is used to indicate the invited study group as a whole, rather than the individuals who actually completed colonoscopy. In addition, 29% of endoscopists had an adenoma detection rate — a surrogate marker for colonoscopy quality — less than the minimum recommended threshold of 25%; as such, the decrease in colorectal cancer-associated death may have been even more pronounced with high-quality colonoscopies. Of note, the Netherlands, one of the countries involved in the NordICC trial, implemented a national screening program in 2014 with clear reduction in colorectal cancer.

Read more than the headline

Unfortunately, we live in a time when many people read headlines rather than the details. Frequently, news media is sensationalized before the facts are fully understood. Having seen the physical and emotional damage that colorectal cancer can cause, I strongly believe in colorectal cancer screening — using both invasive and noninvasive screening tests — as a preventive measure. The controversy surrounding the findings of the NordICC trial highlights the need for careful evaluation before making judgements. In an age where medical misinformation is widespread, this caveat is important for all of us to remember.

Screening of Diabetes.

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People from U.S. ethnic minorities might benefit from screening for diabetes at an earlier age and a lower body-mass index threshold.

The 2021 U.S. Preventive Services Task Force (USPSTF) guidelines recommend diabetes screening for adults (age range, 35–70) with body-mass indexes (BMIs) ≥25 kg/m2 (NEJM JW Gen Med Sep 15 2021 and JAMA 2021; 326:736. However, minority populations in the U.S. (e.g., Black, Hispanic, Asian) have higher rates of diabetes than do white residents. Using the cross-sectional U.S. National Health and Nutrition Examination Survey data, investigators used statistical modeling to estimate diabetes prevalence of U.S. racial and ethnic groups and to determine equivalent BMI and age thresholds for diabetes screening.

Findings were as follows:

  • Prevalence of diabetes in adults (age range, 35–70) was significantly higher among people of Asian, Black, Mexican, or other Hispanic descent than among whites (≈20% vs. 12%).
  • To achieve equivalent disease prevalence from screening people with BMIs of 25 kg/m2, the age threshold for screening was much lower for Asian, Black, and Hispanic people (age range, 20–25) than for white people (age, 35).
  • To achieve equivalent disease prevalence from screening 35-year-old people, BMI thresholds were much lower for Asian, Black, and Hispanic people (BMI range, 18.5–20 kg/m2) than for white people (BMI, 25 kg/m2).

COMMENT

This study demonstrates that many adults of minority descent in the U.S. might benefit from screening for diabetes earlier, at lower BMI thresholds, or both to identify an equivalent proportion of diabetes in those populations. Personalizing screening by race and ethnicity might increase diabetes diagnosis rates and improve health equity.

Screening for rare genetic disorders at a point-of-click

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Institute of Genomics and Integrative Biology (IGIB), Delhi, has the global data of every disease causing mitochondrial mutation and its frequency.

The disease caused by each mutation is checked with the data bank and compared with the population frequency.

Fast and accurate diagnosis of disease-causing mitochondrial genetic mutations is now possible thanks to automation of the entire process of data analysis and interpretation by a team of researchers at the Delhi-based CSIR Institute of Genomics and Integrative Biology.

The comprehensive pipeline developed by a team led by Dr. Sridhr Sivasubbu and Dr. Vinod Scaria of IGIB includes methodologies to sequence mitochondrial genome using next generation sequencing and a software to appropriately analyse and interpret the data at a point-of-click.

Mitochondria, the powerhouses of the cell, are unique in several ways. A cell can have multiple mitochondriae, with each mitochondriae differing from one another by a few variations. This phenomenon is known as heteroplasmy. Heteroplasmy can vary between cells of the same tissue, organ, individual or even between individuals of the same family.

Though heteroplasmic mutations implicated in mitochondrial diseases are seen even in healthy individuals, the reason why they do not manifest as disease is due to low frequency of heteroplasmy. A person does not manifest the disease when the heteroplasmy frequencies are low, usually less than 10 per cent. “Nearly 20 per cent of normal individuals harbour heteroplasmic mutations reported to be implicated in mitochondrial diseases but the frequency is less than 10 per cent,” said Dr. Scaria.

The mutations could also be acquired during cell division. While all cells will carry the mutations associated with disease when it is inherited, cells in different tissues may have different mutations when it is acquired.

Also, compared with nuclear genome, the mitochondrial DNA has a 5-10 times greater rate of mutation than nuclear DNA. “So it is not surprising that mitochondrial disorders are one of the commonest rare genetic disorders, with an incidence of approximately 1 in every 5,000 births globally,” says Dr. Scaria.

Though many hospitals now have the Next Generation Sequencing, doctors do have the expertise to do the entire process of seeing where the mutations are and interpret if the mutations so seen cause disease or not. Also, the frequency of heteroplasmic mutations needs to be known. Many of the so called mutations are common in the population but at a lower heteroplasmic frequency. “If the frequency is more in the population then the mutation is probably not a disease causing one,” Dr. Scaria said.

“We have attempted to close this gap by automation of the entire process of data analysis and interpretation,” he said. First the mitochondrial genome is sequenced using next generation sequencing. To make interpretation possible, the raw data is overlaid on the mitochondria genome and the positions where the variations are present are noted and the frequency of the variation in the sample is also recorded.

The disease caused by each mutation is checked with the data bank and compared with the population frequency.

Since IGIB has the data of all disease-causing mutations and the frequency of every single disease-causing mutation in the global population, comparing the frequency of the sample with the population can be carried out automatically.

“The commercial application of the knowledgebase would enable fast and accurate diagnosis of mitochondrial genetic mutations with implications in clinical diagnosis, prenatal testing and carrier screening,” he said.

This technology has been licensed to the Bengaluru-based Eurofins Clinical Genetics India Pvt Ltd. to enable fast and accurate diagnosis, screening at clinical turnaround times and research into mitochondrial diseases. The service is presently available in India as MitoSure.

The company has been testing samples since mid-April. “We have so far tested 25 families,” said Dr. Surendra Chikara, Executive Director of Eurofins. The cost per test ranges from Rs.15,000-20,000 and has a turnaround time of two weeks.

“We will soon be starting screening campaigns for families with known history of disease-causing mitochondrial genetic mutations. This will help the family to know the female members’ carrier status,” Dr. Chikara said. In this case, the identified mutation alone is screened and cost Rs.5,000 per person.

A person is healthy when heteroplasmy frequencies are low

Colorectal Cancer on the Decline — Why Screening Can’t Explain It All

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Unlike screening for breast or prostate cancer, screening for colorectal cancer promises not only to find cancer early, but also to prevent it from occurring. In the 1960s, Gilbertsen first suggested that polypectomy could turn colorectal cancer into a preventable disease.1 Two decades later, Vogelstein envisioned the polyp-to-cancer progression as a stepwise process and detailed the genetic alterations that occur at each step.2 Colorectal cancer became widely viewed as having a long latency period — providing ample time for both early detection and prevention. Conditions were thus considered ideal for screening to reduce related mortality.

Nine randomized trials summarized in a Cochrane review provide empirical evidence of an effect of screening on both colorectal-cancer incidence and mortality.3 Four trials revealed a 14% reduction in colorectal-cancer mortality and a 5% reduction in colorectal-cancer incidence with fecal occult blood testing, suggesting that early cancer detection is primarily responsible for the reduction in mortality associated with that method. Five trials demonstrated a 28% reduction in colorectal-cancer mortality and an 18% reduction in colorectal-cancer incidence with sigmoidoscopy, suggesting that cancer prevention is the predominant mechanism for its effect. The trial data confirm colorectal cancer’s long latency period by revealing a substantial delay — on the order of a decade — between screening and reduced cancer incidence and mortality.

Against this backdrop, we considered trends in colorectal-cancer incidence and mortality among U.S. adults 50 years of age or older. The big picture is unambiguous “good news”: overall colorectal-cancer incidence has dropped by almost 40% since 1975 and by more than 45% since its peak in the mid-1980s. More important, colorectal-cancer mortality has fallen by more than half

Colorectal-Cancer Mortality (Top) and Stage-Specific Incidence (Bottom) among People 50 Years of Age or Older in the United States, 1975–2012.).

These trends are often attributed to screening. But the magnitude of the changes alone suggests that other factors must be involved. None of the trials of colorectal-cancer screening has shown a 50% reduction in mortality — nor have trials of screening for any type of cancer.

More important, the timing of the trends isn’t consistent with this explanation. Population-wide colorectal-cancer screening has been slow to disseminate into clinical practice. According to the National Health Interview Survey, in 1987 only about 23% of the U.S. population 50 years of age or older had been recently screened.4 Nearly two decades later, in 2005, that rate had increased only to 50%. Given the slow uptake of screening and its expected delayed effect on mortality, it’s hard to imagine a substantial screening effect at the population level showing up much before this new millennium started.

If not screening, what explains the decrease in colorectal-cancer mortality? We believe there are three categories of plausible explanations. First, the treatments available for colorectal cancer today are better than they were 30 years ago. Improved surgical technique, standardization of preoperative and postoperative care, and an increasing reliance on high-volume providers have probably combined to reduce operative mortality. And the addition of adjuvant chemotherapy for patients with regional (node-positive) disease has been demonstrated to reduce longer-term mortality. Even patients with widespread disease can now undergo resection of distant metastases, and a quarter of them survive 5 years or more.

Second, earlier detection of symptomatic disease and subsequent reductions in mortality can occur even in the absence of widespread screening. Patients with colorectal-cancer symptoms are most likely presenting earlier and being diagnosed earlier than they were in the past. The widespread availability and use of endoscopy has lowered the threshold for directly examining the colon in people with symptoms that might represent cancer. Upticks in the incidence of local and regional disease in the late 1970s and early 1980s and again in the late 1990s may reflect the increasing use of sigmoidoscopy and colonoscopy, respectively. The decreasing incidence of metastatic disease — the rate at which patients initially present with metastatic colorectal cancer — is compatible with earlier detection of progressive cancers and is an important intermediate step for reducing mortality.

Finally, there could be fewer cases of colorectal cancer occurring in the first place. The incidence of metastatic disease has fallen steadily and substantially — by 45% since 1975. The decrease in overall incidence began well before the expected effect of polypectomy. In the absence of overdiagnosis, decreased incidence will reliably lead to decreased mortality.

A number of factors may be responsible for the decrease in colorectal-cancer incidence. For a gastrointestinal cancer, an obvious candidate would be a change in diet. Reduced consumption of smoked and cured meats has presumably resulted in lower exposure to carcinogenic nitrosamines. Changes in the gastrointestinal microbiome are another obvious candidate. The widespread use of antibiotics has probably led to changes in gut flora, as evidenced by the decreasing prevalence ofHelicobacter pylori. Finally, the use of nonsteroidal antiinflammatory drugs (including aspirin), hormone-replacement therapy, and statins may have played a role, given their association with reduced colorectal neoplasia.

All of which is not to say that screening has had no effect on colorectal-cancer mortality. The steeper decline in the incidence of both local and regional disease in the past few years may reflect the preventive effects of increased rates of polypectomy. The rate of screening colonoscopy nearly doubled between 2000 and 2005 — from 20% to 39% among U.S. adults 50 years of age or older5— which could well explain this trend.

Nevertheless, we believe it’s important for clinicians to have some humility regarding the effect of screening on disease trends. Although it’s tempting to take credit for good news, doing so may exaggerate the perceived benefits of screening the general population and distract from the more important activities of promoting health — for example, by encouraging a healthful diet and exercise — and caring for the sick. Furthermore, overstating the benefits of colorectal-cancer screening may divert attention from colonoscopy’s downstream effects and potential harms. The majority of people undergoing screening are neither identified as having cancer nor protected from its developing, but they often endure repeated colonoscopy for surveillance of small polyps. Certainly, aggressive efforts to screen and perform follow-up colonoscopy in persons who are most likely too old or infirm to benefit has real potential to cause harm. In questioning the argument that screening is the dominant explanation for decreasing colorectal-cancer incidence and mortality, the example of gastric cancer may be salient: since 1930, without any screening effort, gastric-cancer incidence and mortality have decreased by almost 90%.

No Need for Screening Echocardiogram in Asymptomatic Adults, Study Confirms.

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Echocardiographic screening for structural and valvular heart disease in the general population does not reduce mortality, according to a JAMA Internal Medicine study. The finding, the authors say, “supports existing guidelines that echocardiography is not recommended … in asymptomatic adults.”

In a population-based study, nearly 7000 middle-aged adults in Norway were randomized to screening echocardiography or usual care. About 9% of the screening group had abnormal echo results that required additional testing.

During 15 years’ follow-up, the primary endpoint — all-cause mortality — did not differ significantly between the groups. Secondary outcomes, including sudden death, death from heart disease, and myocardial infarction, also did not differ.

In a subgroup of participants with a family history of early MI, screening appeared to reduce all-cause mortality (number needed to screen to prevent 1 death, 21) — a novel finding that the authors say warrants confirmation.

Source: JAMA