Cancer Screening Debate Continues as New Diagnostic Method Shows Promise
The ability to detect cancers has improved more rapidly than knowledge of which cancers will kill, but a new biomarker test could hold some answers.
By Susan E. Matthews
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WEDNESDAY, September 11, 2013 — Women trying to decide when to start getting screened for breast cancer have faced a more complex decision since the U.S. Preventive Services Task Force (USPSTF) changed their guidelines in 2009, and despite the four years since that change, the debate hasn’t subsided. Even this week, the opinions of scientists conflicted: on Monday, a team of Harvard researchers released a study supporting the importance of screening, but that night, a conference at Dartmouth College began that largely focused on the perils of too much screening.
If doctors are on such opposites sides of this debate, how are individuals supposed to know what course of action is right for them? The question over whether to get screened, and when, spreads beyond breast cancer to prostate cancer, thyroid cancer and beyond, but a study out today may end the debate.
Understanding the Problem
In recent years, screening technology has improved to the point where imaging is so precise that any sort of irregular clump of cells shows up in a screening test. The problem, however, is that even though many of these irregularities look like they could be cancer, not all of them will actually turn into cancer or become dangerous during the person’s lifetime. “We assume that because it looks like cancer, it is going to kill,” said Otis Brawley, MD, FASP, chief medical officer for the American Cancer Society.
The problem of overdiagnosing cancers was summarized by Steven Woloshin, MD, professor at the Dartmouth Institute for Health Policy and Clinical Practice, at a conference this week on Preventing Overdiagnosis. Dr. Woloshin recalled a quote from a radiologist who had screened more than 15,000 patients for cancer. “The realities are, with this level of information, I have yet to see a normal patient,” the radiologist said.
Because it’s so difficult to tell how a presumed cancer will progress, people who have these irregularities are often aggressively treated. The impulse to treat these sorts of diseases doesn’t only come from doctors, either — .
“The goal is not to find more cancer, but to reduce deaths,” said Woloshin at the conference’s opening plenary.
The result of increased screening is that many people are undergoing procedures that are unnecessary, costly, and could be harmful, either physically or emotionally, and for this reason, in 2009, the USPSTF adjusted their recommendations on breast cancer screening to reflect that. The updated recommendations suggested women wait to be screened until age 50, rather than 40, unless their doctor recommends otherwise. The change came after the USPSTF realized that “the benefits outweighed the harms, but only by a small amount,” said Michael LeFevre, MD, MSPH, co-vice chair of USPSTF. “In the context of that, we thought that women should engage in a discussion rather than just being told what to do.”
However, the recommendations were met with severe backlash. “What the USPSTF did flabbergasted us,” said Blake Cady, MD, professor emeritus at Harvard, and an author on a study released on Monday in Cancer, the journal of the American Cancer Society. The study is a failure analysis on 609 women who died from breast cancer, a concept that Cady likened to listening to a black box inside an airplane to discover what went wrong. The researchers found that 71 percent of the women who died had not participated in screening.
“The basic message is if women are in screening programs and develop cancer, they largely avoid the disaster of death,” said Cady. “If women are not in screening programs and develop cancer, they largely do experience death.”
Dissecting the Science
Cady pointed to the fact that mortality rate from breast cancer began to drop in the early 1990s, when screening for breast cancer had first been introduced. “There’s nothing else going on than the huge upsurge in screening — no magic drugs,” he said.
Cady noted that his study found that for every age decade they studied, “the majority of women who died of breast cancer were not in screening,” he said. The biological basis of the decision to screen, he added, is that the “disease has a progressive biological course so you can interrupt it throughout the way and avert disaster.” The study also found that 50 percent of deaths occurred in women under 50, when the USPSTF doesn’t recommend women be screened.
The problem, however, is that women who are going to get breast cancer before they’re 50 years old often get a very aggressive form of the disease, said Brawley. He likened it to a burglar robbing a home, where stealing everything means the person is dead. Someone who steals very quickly (the aggressive cancer common in women under 50) is less likely to get caught, while a slow burglar could be caught in time to warrant treatment. “Younger women have very fast-growing cancers where no intervention is going to be helpful,” he said.
Brawley said that most of the research he’s seen on breast cancer shows that 80 to 85 percent of women with breast cancer “would still die even if they got regular screening.” This means that the debate over whether to screen narrows in on the other 15 to 20 percent of women, which is ultimately a small population, particularly when considering the large number of women who could be harmed from excessive, unnecessary treatment.
Developing a Better Method
Researchers on both sides of the debate pointed out technical problems with the other sides’ research papers, but ultimately, the debate centers on how many false diagnoses are worth a life saved by screening, which is largely a matter of personal belief and preference. Fortunately, a new piece of research out today from Columbia University points to a new way forward. Rather than offering insight on whether or not to screen, the paper shows an option for making screening more effective.
“The devil is not in the screening, it’s in our understanding of what that screening tells us,” said lead study author Cory Abate-Shen, PhD, professor of urological oncology at Columbia University Medical Center.
In the study, published in Science Translational Medicine, the researchers pinpointed three genes that indicate how dangerous early prostate cancer is likely to become. Testing for the presence of these biomarkers could help doctors have a better indication of when to pursue aggressive treatment, and when to suggest active surveillance. The researchers found tested genes in the prostate cancer of mice, and then used a computer program to pinpoint three genes — FGFR1, PMP22 and CDKN1A — that would provide a clear indication of severity. The researchers then tested for the presence of these genes retrospectively in 43 patients who had been diagnosed with low-risk prostate cancer. The test correctly identified the 14 patients whose tumors progressed to advanced prostate cancer.
While the idea still needs to be tested prospectively and in larger groups, the initial results are promising, said Dr. Abate-Shen. “It helps the clinician who’s reading the biopsy to say ‘this is a bad tumor,’ with confidence,” she said, and it same process could work for other cancers.
“This concept of sorting tumors — sorting bad and good players based on enrichment of genes — held up in both breast and lung cancers,” Abate-Shen said.
Both Cady and Brawley were cautiously optimistic about a new screening tool. Cady warned that there may never be a perfect biomarker, but emphasized the improvements to cancer treatment could work to make up the difference.
Video: Debate Over New Guidelines for Breast Cancer Screening
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