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he best-known downside of cancer screening, such as PSA tests for prostate cancer and mammograms for breast cancer, is that they often flag cancers that pose no risk, leading to overdiagnosis and unnecessary, even harmful, treatment. But widespread screening for “scrutiny-dependent” cancers — those for which the harder you look the more you find, and the more of what you find is harmless — causes another problem, two leading cancer experts argue in a paper published on Monday: increasing the apparent incidence of some cancers. That in turn is misleading doctors and the public about what increases people’s risk of developing cancers — or at least the types of cancer that matter.

“Detecting cancers that would never become apparent is screwing up our understanding of risk factors,” said Dr. H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice, co-author of the analysis in Annals of Internal Medicine.

The problem is especially clear in prostate, breast, and thyroid cancers, all of which are scrutiny dependent.

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Men whose relatives developed prostate cancer are more likely to get PSA and other screening tests, either because they request them or because their physicians, noting their family histories, order them. Men with no such family history are less likely to be screened. Some men who get screened for prostate cancer and who are found to have elevated PSA levels undergo a prostate biopsy; some of those biopsies find cancer. (More than half of such cancers are so slow-growing that they don’t affect health or longevity.) Men who don’t get screened are less likely to have biopsies and so are less likely to be diagnosed with prostate cancer — not because they develop the disease at a lower rate but because they get screened at a lower rate. What you don’t look for, you don’t find.

“If we biopsied men without a family history of prostate cancer at the same rate that we biopsy men with a family history, we’d find more prostate cancer in them as well,” Welch said. “Family history influences how hard we look for prostate cancer and therefore how much we find. The risk factor becomes a self-fulfilling prophecy.”

A 2016 study of increased prostate cancer screening in men with a family history of the disease concluded that the risk due to family history has been overestimated by nearly half. “The risk factor of family history is spuriously strengthened because men with a family history are exposed to greater scrutiny,” write Welch and Dr. Otis Brawley, chief medical officer of the American Cancer Society, in the Annals report.

“There is a flaw in this logic” of identifying risk factors “on the basis of how many cancers we find,” agreed Dr. Peter Albertsen of UConn Health, an expert in prostate cancer.

In breast cancer, women who live in neighborhoods with the highest 20 percent of education and income are twice as likely to be diagnosed with that disease, a 2017 study found. That seemed to confirm reports of breast-cancer hot spots in some of America’s wealthiest areas, leading the government and others to spend tens of millions of dollars to find out why. Those studies came up empty: they found no association between rates of breast cancer and proximity to a hazardous waste site or pesticide exposure, for instance.

Wealthier, better educated women are, however, more connected to the health care system and therefore get more mammograms, breast ultrasounds, and MRIs. The more scrutiny, the more likely that harmless cases of breast cancer are found. (The idea of “harmless” breast cancer sounds like an oxymoron, but an estimated one-half of breast cancers detected by screening would never cause problems even if undetected and untreated.)

Breast tumors found by imaging are much more likely to be harmless than those discovered by women or their physicians finding a breast lump. Income and education are therefore less likely to be a true risk factor for breast cancer and more likely to be a “risk factor” for undergoing screening. If poorer, less educated women were screened for breast cancer at the same rate as wealthier, better educated women, the socioeconomic risk factor would likely vanish.

Thyroid cancers are also scrutiny dependent, which is why when countries launch screening programs the incidence of the disease skyrockets (but death rates don’t, showing that what’s being found is a false epidemic). In the U.S., women are about three times more likely than men to be diagnosed with thyroid cancer.

But the two sexes die of the disease at almost identical rates. Just as with prostate and breast cancer, that suggests we’ve been misled about the true factors that cause thyroid cancer, Welch and Brawley argue: women, who see doctors more than men, are more likely to be checked for thyroid cancer, more likely to have nodules detected and evaluated, and more likely to be diagnosed with small, indolent thyroid cancer. If men were screened as effectively for thyroid cancer at the same rate as women, sex as a risk factor for this cancer would likely disappear.

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“They make good points,” said epidemiologist Noel Weiss of the University of Washington and the Fred Hutchinson Cancer Research Center. “There are circumstances where the rate of screening makes a difference” in how many cancers are detected and therefore in what seems to be a risk factor, “especially in thyroid and prostate cancer, where there is a large burden of hidden [harmless] disease.”

Welch and Brawley call for less focus on risk factors for developing cancers, since those numbers both determine and reflect who gets screened, and more on risk factors for death from cancer. “Death from disease or incidence of metastatic disease is probably more accurate and appropriate,” agreed UConn’s Albertsen, since both are “hard outcomes” not subject to what people choose to do.

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  • – for ever one extra life saved by screening mammograms, TWO women will be overdiagnosed and overtreated, i.e., will receive surgery, chemotherapy, and/or radiation when they didn’t need it, and that treatment can cause harm
    – overdiagnoses occurs at a rate of between 11 and 22%
    – if a woman adheres to the standard screening schedule she has a roughly 50% chance of having at least one false positive
    – false positives can cause great stress and often necessitate repeat mammograms and invasive biopsies
    – as many as 46% of women who experience pain during a mammogram refuse to have another (telling us that mammograms are very painful for some women)
    – radiation from mammograms increases a woman’s risk of breast cancer

    “The small probability that a woman may avoid a breast cancer death must be weighed against the more likely scenario that she may have a false-positive result and possible unnecessary follow-up testing (including invasive testing); a false-negative result, with false reassurance or delayed diagnosis; or most critically, diagnosis and treatment of cancer that would otherwise not have threatened her health or even come to her attention. Women who value the possible breast cancer mortality benefit more than they value avoiding the harms can make an informed decision to begin screening.”

  • https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening1
    https://www.ncbi.nlm.nih.gov/books/NBK343818/#ch4.s1

    – for ever one extra life saved by routine mammograms, TWO women will be overdiagnosed and overtreated and will receive surgery, chemotherapy, and/or radiation when they didn’t need it, and that treatment can cause harm
    – overdiagnoses occurs at a rate of between 11 and 22%
    – if a woman adheres to the standard screening schedule she has a roughly 50% chance of having at least one false positive
    – false positives can cause great stress and often necessitate repeat mammograms and invasive biopsies
    – as many as 46% of women who experience pain during a mammogram refuse to have another (telling us that mammograms are very painful for some women)
    – radiation from mammograms increases a woman’s risk of breast cancer

    “The small probability that a woman may avoid a breast cancer death must be weighed against the more likely scenario that she may have a false-positive result and possible unnecessary follow-up testing (including invasive testing); a false-negative result, with false reassurance or delayed diagnosis; or most critically, diagnosis and treatment of cancer that would otherwise not have threatened her health or even come to her attention. Women who value the possible breast cancer mortality benefit more than they value avoiding the harms can make an informed decision to begin screening.”

  • Ms. Begley states: “Breast tumors found by imaging are much more likely to be harmless than those discovered by women or their physicians finding a breast lump.” “Harmless” isn’t a word I would use to describe breast cancer but she is right about one thing. Breast tumors found by imaging are smaller and treated with less invasive and less costly therapy and less likely to kill patients than those found by women or providers finding a lump. These are the benefits of screening.

    Breast cancer overdiagnosis is nowhere near “half” as Ms. Begley suggests. The link she provides leads to the Canadian screening trial and suggests a much lower rate. I encourage Ms. Begley to read a study from Denmark by Njor et al, that used data linked to real patients and calculated a 2.3% rate of overdiagnosis. (Njor SH et al. Overdiagnosis in screening mammography in Denmark: population based cohort study. BMJ. 2013 Feb 26;346:f1064. doi: 10.1136/bmj.f1064.)

    Ms. Begley invites to discuss “hard outcomes” such as death from breast cancer. Indeed, those of us who detect and treat know that deaths from breast cancer have dropped 35-40% per year since screening mammography became widespread. In Canada it is 40% (Coldman A et al. Pan-Canadian study of mammography screening and mortality from breast cancer. Journal of the NCI 106.11 (2014): dju261.) which means thousands of real lives saved. This, as Ms. Begley indicates in her final paragraph, is a “hard outcome” that we can all be grateful for.

    • You say deaths have declined. But you need to consider that you in all likelihood overtreating. For every 1 extra life saved through screening, 2 women will be overtreated. Imagine being one of those women, being told you have cancer, going through all of the extra diagnostics, then being treated with surgery, chemo, radiation, and then proudly declaring yourself a “survivor” even if you feel half dead. How would you feel if you later found out that you didn’t need any treatment at all?

  • The article by Sharon Begley “Too much screening has missed us about real cancer risk factors, experts say”
    is based on “Alternative Facts”. It is astonishing and worrisome that a whole alternate universe has been created by those claiming that there are tens of thousands of breast cancers that would disappear if left undetected by screening. No one has ever seen a breast cancer detected by mammography “disappear” without treatment. The article quotes “experts” who do not provide care for women with breast cancer and, themselves, have never seen a breast cancer detected by mammography disappear on its own. The mythology is based on scientifically unsupportable analyses that have made it past biased and poor quality peer review to get published. A recent review of almost 500 breast cancers detected by mammography that had not been treated showed that none “regressed” or “disappeared”.

    The treatment of Ductal Carcinoma in Situ (the earliest form of breast cancer) – DCIS – is a legitimate area of discussion since it may take many years for these lesions to become invasive and potentially lethal, but invasive breast cancers grow and have lethal potential. The most rigorous scientific studies, randomized, controlled trials, have proven that, although not perfect, detecting breast cancer earlier by screening saves lives. In fact, screening is the main way that lives are saved. Once a breast cancer is metastatic (spread to other parts of the body) it cannot be cured. Treatment can help to delay death, but if something else does not kill the woman she will, ultimately, be killed by her breast cancer.

    There is no guarantee that anyone diagnosed with cancer will die from the cancer. Some huge breast cancers are simply a nuisance while the woman dies, ultimately, from some other cause. Someone diagnosed with any cancer may be killed in a car accident. That does not mean that cancers should not be treated. In fact, ALL breast cancers (including those that can be felt in the breast) are “overtreated”. We are getting better at identifying who will benefit from treatment, but we are still unable to be very accurate. It is fine to argue that we need to be more accurate, but if we are unable to do this right now, it is simply wishful thinking.

    There is NO EVIDENCE that invasive breast cancers detected by mammography have any less potential to kill than when they grow larger and become lumps that can be felt. It is well established that the larger a cancer the greater chance that it has already spread to other parts of the body (metastatic) and become lethal.

    It is time for the nonsense to stop. Lives are at risk, and the dissemination of misinformation is endangering women. We need to constantly improve our understanding of all aspects of health care, but breast cancer screening has been studied from every direction and shown to save lives.

    This article does raise the question of the importance of risk factors and this is legitimate. In fact, the vast majority of women (75%) diagnosed with breast cancer do not have any known elevated risk. Concentrating screening on high risk women will mean that most women will not have the advantage of screening.

    It is outrageous that medical publications are failing in carefully checking the science behind what they are publishing, but the media need to be more skeptical. The death rate from breast cancer has declined dramatically since the start of screening. Therapy has improved, but breast cancer is only cured when it is treated early. Unfortunately, many of the 40,000 women who still die each year despite improvements in therapy are likely not participating in screening.

  • Good points here. I’ve had two cancers so far (that I now of), and neither was found by routine costly screening, but both were found by observation. I am hoping to hold the line. What I do suggest, based on personal and family experience, broadening that circle to others, and a fair amount of open ended, multifaceted questioning, research and investigation, are the following.

    First, periodic screening for dental, root canal, jaw and lymph infections. They can be fairly asymptomatic for years, but can serve as a motherlode, and can have impacts far before anything is visible on xray. Second, screening for mold exposure, especially for those who have genetic susceptibility to mold toxicity; it places a big drag on the immune system, and is terrible on the lungs. Third, a general approach to cleaning up one’s microbiome and biological terrain so it is a little closer to what mother nature intended, vs. the excesses and impacts of living, breathing, and ingesting in a fairly unnatural world. Pay special attention to the inner as well as outer environment, as medical and dental devices are a 24 7 365 source of exposures that just might not be right for you and your immune system, yet are commonly overlooked and given a free pass in our health and medical system. Given we can’t retroactively change our histories, we do well to prospectively improve the odds for our immune systems in our futures.

    • One of my rescue cats had long term dental problems, and probably had very poor foods as a kitten. She did not receive the annual or bi-annual cleanings she needed, and finally, at about 8 years, needed all her teeth removed. Many were severely decayed and infected. She probably had organ damage due to the constant infections. During the dental surgery, she had a heart problem, and the vet stopped surgery with only half of her teeth removed. It took about 8 months for me to save enough to even consider the next round of work which would have included a cardiologist. Sadly, she had developed oral cancer that was close to blocking her throat and had to be put down. The vet said the cancer was almost certainly the result of the long term decay, inflammation,and infections from not having dental cleanings and extractions every year or two. She probably had long term organ damage from the infections as well. So, she’s a cat; how is this relevant? She demonstrates that dental health can severely affect overall health. The difference is that (hopefully), even very poor people can at least get rotten teeth removed, thus preventing the long term organ damage and inflammation she suffered. If those teeth are not removed, long term results can be dire, even leading to cancer. (And if you have a pet, you may be able to get affordable dental care; a clinic in Richmond, Va offers dental work at app $250/cat or dog; check vet schools etc.)

    • Denise, thank you. I could have written that same story about my cat.

      However, for those with weaker immune systems due to the draw of the gene lottery, or a history of other exposures that weaken it over time, even routine, regular, standard dental cleanings, care and restorative work is not sufficient and no guarantee.

      I could have written the same story about my mother. Someday I will.

      Biological dentistry – that is cognizant of immune, galvanic and toxicological impacts of dental materials, and does better screening for dental infections that can drain to the jaw and lymph system years before they are visible on xray – has the potential to prevent and assist treatment for certain cancers. There is emerging evidence on connections to certain breast and lymph cancers.

      Until primary care doctors, allergists, cardiologists, GI specialists, neurologists, rheumatologists, and oncologists look in, ask about, and enter or review data on dental and oral health (including tooth status and dental materials into our medical records) – all the AI, Big Data, Precision Medicine and cancer screenings in the world are doomed to fall short. They are at best a rear guard action – conducting analysis and plotting a trajectory for treatment with half a deck and some key coordinates missing – vs. preventive or protective.

      During each office visit, many patients are asked to update their Rx and OTC list. Why not add a dental and medical device list? Teeth, dental and medical devices and materials are with us 24/7/365, so pay more attention.

  • Dr. Gordon is correct. Only 25% of all breast cancers are associated with women at higher risk for the disease (family history, personal risk factors including genetic mutations). 75% of all breast cancers occur in women at average risk. If we screened only the higher risk population we would miss 75% of all breast cancers.

  • Every year, thousands of lives are saved because of “scrutiny”. Over diagnosis is not the issue. For decades I and others, including the leadership of Dr Albertsen, have been trying to emphasize over treatment. In prostate cancer, having a PSA. Is “just a test that needs to be interpreted wisely”. It IS NOT A SLIPPERY SLOPE TO RADICAL THERA PY. I have been practicing active surveillance for almost 20 years and have saved well over a thousand men the trauma of radical treatment. But a high risk cancer discovered while still localized to the organ of origin, cannot and should not be ignored. Dr Welch, please look at these cancers through the lens of morbidity and mortality, not just mortality. You are rendering a disservice to all men and women with the opportunity to decide what is ultimately best for them. Physicians everywhere, understand that the issue is solely overtreatment and decisions along the biological runway of cancer biology,nfrom the point of prevention all the way to palliative care demands an informed patient. Until we have the crystal ball available to predict biology, the onus is on us to care with our hearts as well as our statistics.

  • The randomized trials of screening mammography, although acknowledged to underestimate the benefits, showed significant mortality reduction. And this is confirmed with observational trials. None of the RCTs stratified by risk. The greatest risk for developing breast cancer is being female, and the second is getting older. Annual mammography starting at 40 saves the most lives. Women at higher than average risk, such as those with dense breasts, should have additional supplementary screening.

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