13 January 2016

The Confounding Commandments Of Cancer Screening

Article re posted from http://www.popsci.com/confounding-commandments-cancer-screening

Mammogram

These are images generated from a mammogram, a breast cancer screening test.

Last year, at the age of 43, Chicago-based writer Jessica Gardner had her first mammogram. She knew that most screening guidelines recommended that women of average risk for breast cancer receive annual mammograms starting at age 40, but Gardner procrastinated—because she didn’t have insurance when she turned 40, and because she was scared, she says. “When I was 41, my mom had breast cancer, and that scared the bejeezus out of me,” Gardner adds.

Once she got the mammogram, the radiologist saw an area of concern—there were some calcium deposits inside the breast tissue and, while it’s not uncommon, the doctors wanted to get a better look. There were more scans, a biopsy, and eventually a lumpectomy for some tissue that could become cancerous over time. Though Gardner considers herself of average risk for breast cancer, she is now a staunch advocate for breast cancer screening; in 2014, she wrote a blog post titled, “My first mammogram saved my life.”

Recently, the American Cancer Society changed its breast cancer screening guidelines; women should get annual mammograms starting at age 45, instead of at age 40. The U.S. Preventive Services Task Force, the other major organization that makes these recommendations, announced this week that it intends not to change its guidelines, recommending that a woman start thinking about breast cancer screening at age 40 based on her individual health profile, but definitely start screening by age 50. Though screening for cancer is just one tool in the increasingly sophisticated field of cancer prevention, early detection of breast cancer, like many other types of cancer such as those in the prostate and lung, could be essential for doctors to treat the disease before it threatens a patient’s life.

For women thinking about when to start screening for breast cancer, weighing the different guidelines can be a confusing and difficult experience. Most women want to know: Should I start at 45 or 50? Should I be screened every year or every other year? Am I ever supposed to stop? What is “average risk,” and do I have it?

Each organization gives a slightly different or nuanced answer to each of those questions. Why can’t experts agree on when to start screening and how often it should be done? What are the risks of over-screening, and, most importantly, how are patients supposed to parse through the noise to do what is right for them as individuals?

Why can’t experts agree?

The goal of cancer prevention is simple: prevent a patient from developing the disease, or dying from it. The field really took off in the 1990s, when public health officials urged people to stop smoking in order to prevent cancer, says Therese Bevers, the medical director of the MD Anderson Cancer Prevention Center and the chair of the National Comprehensive Cancer Network’s panel that creates guidelines for breast screening.

Screening tests are usually done on patients who don’t have symptoms. Doctors hope that, if screening is done consistently, it will catch lesions and polyps that may become cancerous. For some types of cancers, such as those in the cervix or colon, removing those non-cancerous growths early can mean that a patient never develops cancer at all.

“The general intent of screening is to catch disease early so that the treatment is less intensive, and then lower the chance of dying from cancer,” Bevers says.

Preventing cancer seems very straightforward, at least in the abstract. But every patient is a little different, with different family histories and past illnesses and lifestyle or risk factors. Those all affect a person’s likelihood of developing certain cancers over others, and can make it difficult for doctors to know which types of cancers to watch out for.

These guidelines are intended to provide patients with recommendations for cancer screening--what kind of screening, when to start, how often to get it--that will best help them prevent cancer. Insurance companies also use the guidelines to decide whether or not they will cover a patient’s screening. If people don’t screen for cancer early or often enough, there’s a greater chance that disease could grow unchecked, making it harder to treat later. Screen too much, though, and patients could overburden doctors, expose themselves to possibly harmful radiation, or undue stress. And though different organizations and agencies sift through dozens of scientific studies to create guidelines that streamline the science to best guide the public, the conflicting guidelines themselves might end up confusing more people than they help.

Making The Guidelines

Screening guidelines can provide a place to start for patients with average risk for certain types of cancer. Before issuing its screening guidelines, a committee of experts looks at scientific studies to determine what has been proven to work best for patients. They consider all the different technologies for screening (for breast cancer, they would weigh the evidence for mammograms versus self-exams) and only consider cancers in a particular region of the body. The committees want to know if patients lived longer if they received cancer screenings. If they did, how often should they get them, and at what ages are they most beneficial?

Randomized controlled trials—experiments that compare the health outcomes for randomly chosen patients who received the treatment to those who did not—are considered the highest quality evidence. Ideally, these trials would include hundreds or thousands of patients. But these trials are very expensive and take a long time, so there aren’t very many of them. It can be limiting to only consider these, says Kirsten Bibbins-Domingo, a professor of medicine at the University of California San Francisco, and the vice chair of the U.S. Preventive Services Task Force.

Many organizations take other kinds of studies into account, including observational studies, trials in which researchers track patients who received the treatment and those who didn’t to see if the treatment helped them live longer. Since the researchers aren’t trying to alter the outcomes themselves, these experiments can be done more quickly, which can help experts get a quicker assessment of new treatments. That can be useful, especially if the studies are done well, but they are considered weaker evidence than the randomized controlled trials—the researcher is only looking at one variable among many, and she is not herself adding an experimental variable. So these studies can’t absolutely determine the cause of an outcome, only what it’s likely to be based on correlation data.

Breast cancer from a mammogram

These mammogram images show a healthy breast, left, and a breast with cancer, right.

Why do different organizations issue different screening guidelines? In some cases, they’re not using the same studies, so it’s only natural that these organizations would reach different conclusions. For their breast cancer screening guidelines in 2009, the Task Force didn’t consider observational studies, Bibbins-Domingo says. But in response to public feedback, the organization has since incorporated observational studies.

Even while looking at the same evidence, however, experts can sometimes disagree. They may interpret the study’s findings differently, or, if two similar studies had disparate conclusions, they may find one more convincing than another based on the type of data or the study design. “If you look to experts in the field to see what they’re saying, there’s going to be disagreement still,” Bevers says. “But it’s important to get an understanding of why they disagree. It may be that there’s things they agree on.”

Why Not Just Screen As Much As Possible?

“Screening is a very blunt instrument in some ways,” says Robert Smith, the vice president of cancer screening at the American Cancer Society. "Screening tests are not diagnostic tests.” Though screening tests target the cancers that have higher mortality rates, doctors can sometimes uncover other cancers in the process. But the tests don’t show doctors if a cancer will progress or not. It’s then up to the doctor and patient to talk about treating the cancer, especially if it’s at an early stage.

Too-frequent screening comes with its own set of concerns. Despite years of debate, the low levels of radiation exposure involved in screening tests like mammograms, is no longer a big worry (the scientific consensus is that the benefits of screening far outweigh the risks), though the same may not be true for CT scans used to diagnose other types of cancers and to make 3D images of the breast. Some tests have a high rate of false positives, which cause patients unnecessary distress. One 2012 study estimated that around 20 percent of women will get a false positive result from a mammogram; earlier studies found even higher numbers.

MRI image

False-color MRI images like these aren't typically used for breast cancer screening, but they can provide more detailed images of the breast, which is useful for high-risk patients.

Even regular screening tests can lead to overdiagnosis, the diagnosis of condition that wouldn’t otherwise go on to threaten a patient’s life. “The real value of screening is in that early detection [of disease]. But that often leads to detection of other things that wouldn’t have caused a problem,” says Bibbins-Domingo. One study, published in August in JAMA Oncology, followed 100,000 women over 20 years and found that treating patients for the earliest stages of breast cancer didn’t make them any less likely to die from advanced stages of the disease.

As a result, doctors and patients feel compelled to treat the condition, and that’s not always what’s best for a patient, says Laura Shepardson, the associate director of breast imaging at the Cleveland Clinic. “When we catch disease early, we hit it with the biggest cancer treatment we have. And those can cause significant comorbidities [co-existing conditions] for a patient,” she says.

Treating a condition is not always what’s best for a patient.

There are dangers in using very aggressive treatment on such early stages of disease. Sometimes, radiation or chemotherapy used to treat these conditions can set the stage for cancers to develop later on. Preventative surgeries can have grisly side effects—men who have their prostates removed, for example, may be incontinent and impotent for the rest of their lives. And while some patients may be tempted to go under the knife at the first sign of disease, it may be more prudent to wait; while some types of prostate cancer progress quickly and cause thousands of deaths per year, overall men are more likely to die with prostate cancer than from it.

For all these reasons, organizations like the American Cancer Society and the Task Force are cautious with their screening recommendations. “There are trade offs between vigilance and precaution, and not wanting you to be overly preoccupied,” Smith says.

Overdiagnosis and overtreatment have been making headlines lately. “This concern is prompted by more studies that have come to light, as well as more discussion about what they mean, has led to an era where many things are shifting,” Bibbins-Domingo says. “We are living in a time when there is more aware of overtreatment. There’s more discussion among people who are doing treatment about what is the appropriate approach, when we should treat, et cetera.”

But not everyone agrees that overdiagnosis is a problem. “Careful studies that adjust for trends and incidence find very low rates of overdiagnosis,” he says, estimating a woman’s absolute risk of having an overdiagnosis of breast cancer at about one percent. The advantage, he adds, is that such early-stage cancers are much more treatable, giving a patient a better prognosis than a disease that’s even slightly more advanced.

If a physician catches early signs of cancer during a screening, for some low-risk patients the best recourse may be to continue screening more frequently and treat it only if the disease progresses, a tactic called watchful waiting. And though screening has undoubtedly saved or extended thousands of lives, it’s still not an exact science. And doctors and scientists alike still have a lot of questions that need to be studied before it can become more precise.

For example, many breast cancer experts are focusing on a condition called ductal carcinoma in situ (DCIS), in which abnormal cells line the milk ducts in the breast. It’s considered to be the earliest stage of breast cancer and doctors prescribe lumpectomies and other preventative treatments when they catch it (though she received the same treatment, Gardner had a different pre-cancerous condition). But they’re still not sure that DCIS is in fact a precursor to breast cancer, or that treating it does a patient any good. “Do we know for a fact that diagnosing DCIS is an overdiagnosis for breast cancer? We don’t have that answer yet. We may need to look at the disease differently,” Bevers says.

The Future Of Cancer Screening

Screening has come a long way in just a few decades (it’s been 40 years since mammograms became standard practice), producing high-quality images that help doctors treat patients. But it can still do better.

Researchers and biotech companies striving to reduce overtreatment and overdiagnosis come out with new screening tools all the time. But before they make their way into local hospitals, those tools need to be vetted by experts to ensure that the technology offers demonstrable benefits to patients. Tomography, which produces 3D images of the breast in addition to a conventional mammogram, is one such tool. Initial studies indicate that it’s pretty useful—it produces sensitive images that can reduce the number of patients who are called back for additional screening, saving doctors time and reducing patient anxiety. But researchers are still debating tomography’s benefits in the long term. “We’re figuring out how much better [tomography] might actually be,” Smith says.

3D mammography

Digital breast tomosynthesis, or tomography, gives doctors a 3D look at a breast, making it easier to catch pre-cancerous growths.

Patients could receive better diagnosis and treatment without any new screening tools, if the systems could shift. In countries with nationalized healthcare systems, government organizations remind patients to get periodic screenings, ensuring that patients follow the recommended guidelines (some insurance companies in the U.S. do this, too, but it’s less consistent). Smith notes that a centralized screening organization could compile patients’ results in one place, providing researchers with data that could point to trends in patients’ risk factors, especially among underserved populations that don’t usually participate in clinical trials. It could even reveal weak points in screening practices—though images generated from screenings are fairly standard, radiologists’ interpretation of those images is still not consistent.

Even if screening were reorganized dramatically, there’s little doubt that more clinical trials are needed. Experts still have some fundamental questions about how cancer grows and spreads that need to be answered if screening—and early stage treatment—is to become more perfect. Is there a way to determine which early-stage cancers will progress into life-threatening diseases, and which will remain harmless? “We need to understand the diseases better—once you understand which will progress and which will not, then you can say this [pre-cancerous condition] isn’t the problem and doesn’t need to be treated,” Bevers says.

Some researchers think that precision medicine, a field that uses genetics to better identify and target cancer-driving mutations, could hold the key. The Holy Grail, from a screening perspective, would be finding a biomarker. With a simple blood test, that biomarker could show doctors that a patient runs a higher risk of developing a certain type of cancer, or could even help detect tumors before they can be seen in other screening tests. Ideally, it would be cancer-specific, not site specific—a particular type of breast cancer, not just cancer in the breast. To start to answer those questions, Bevers says, scientists need to conduct long-term, large-scale clinical trials. And those take a lot of time and money that, despite the billions of dollars spent annually on cancer research, are often not feasible.

Dense breasts

Typical mammograms can't tell doctors much about dense breast tissue, in which breast cancer incidence might be higher, but the correlation is still unclear.

Given the information currently available, though, screening guidelines are less contradictory than they may appear. It may be easier to pick out the differences between screening guidelines suggested by the ACS and the Task Force, Bibbins-Domingo says, but the similarities are more useful because they highlight the fundamental principles that steered the experts to make them. “Where there are differences in guidelines, try to understand the underlying decisions about the recommendations,” Smith agrees.

As medicine becomes increasingly individualized, it’s more important to remember that recommendations are guidelines, not gospel. And because of how science works, the rules for screening may never be as firm as some might like. “The public needs to be reminded that science changes—we learn new things when we get new data. It’s iterative, and we learn things as we go along,” Smith says.

The best thing anyone can do is to understand the risk factors as we know them and talk to a doctor. If a woman believes she may have a higher risk of developing breast cancer, she should get her doctor’s opinion about starting to screen for it earlier, no matter what any guidelines tell her. “Women don’t make decisions [about screening] once in their lives, and each time those decisions are complex,” Bibbins-Domingo says. “We hope that women and their healthcare professionals are able to engage in this process to make the decision is right for them.”

“The only person who is going to advocate for your health is you,” Gardner says. “It’s our responsibility to take charge and to get the tests we need to sleep at night.”

Last month, Gardner had another lumpectomy, this time on her other breast, because her doctors found a small tumor inside her milk duct. The tumor was benign, but her doctors told her that over time these things can often turn into cancer, so she didn’t hesitate to get it removed. “I’m really grateful that they were able to find this because of mammography and other tests they did,” she says, adding that she intends to continue to get her annual mammogram. “If it had to sit there for a few more years, who knows what would happen.”



Published by
Read more
Post a Comment