Cancer Arises from Stress-induced Breakdown of Tissue Homeostasis

Part 1: Context of Cancer Research

The article is in four parts, following the structure of this overall abstract:

Abstract

Part 1:  I critically review the context of cancer research, where it has been advanced that most published research findings are false, that medicine itself is the third leading cause of death in the Western world, and that experienced stress arising from an individual’s position in society’s dominance hierarchy is the primary determinant of individual health.

Part 2:  I critically review the randomized trials for treatments and screening, especially for breast cancer. It has been advanced that screening does more harm than good, and that treatment protocols have little effect on net population mortality from cancer. There is no robust demonstration that the treatment protocols for the common cancers do more good than harm to individual patients.

Part 3:  I critically review the mutation-centric metastasis dominant paradigm of cancer, and various efforts to somewhat or definitively challenge the dominant paradigm, with an eye to answering the question “What is cancer?”

Part 4:  I propose a conceptual model of cancer, which incorporates the leading criticisms of the dominant paradigm, and which is testable. In my model, cancer is an age-dependent and tissue-specific stress-induced breakdown of tissue-shape homeostasis. My model is aided by a graphical picture depicting age-specific and tissue-specific curves of steady-state nodule size (DT) versus experienced stress level (S). A given curve has a critical stress (SC) beyond which there is runaway tumour growth due to tissue-response feedback. Here, “metastasis” is the simple consequence of the individual’s tissue susceptibility to loss of shape homeostasis having gone supercritical for a cluster of tissue-specific DT v. S curves. The model provides treatment strategies on three branches: Psychological, tissue-surface-shape homeostasis, and tumour growth feedback attenuation.

Introduction

This paper was presented in the uOttawa Cinema Academica series at the University of Ottawa on November 21, 2015. ((Video of the presentation is on the film maker’s YouTube channel, in two parts, here and here)) A pdf version is available on ResearchGate. ((PDF on ResearchGate))

I am not a medical doctor. I am an interdisciplinary scientist with a PhD in physics. I have published over 100 articles in scientific journals, in a broad array of disciplines. ((Google Scholar profile))

My starting outlook in researching cancer is best represented by these three non-journal-article publications:

Context of Cancer Research

Approximately 30% of us who are fortunate enough to live in the Western countries will be diagnosed to have died of cancer. Breast cancer is the main life-threatening disease affecting women, when tumours are present on several organs.

Prior to starting this review to find out what establishment science actually knows about cancer, it is important to admit the possibility that medicine is largely a pack of lies, the usual kinds of lies that provide the mental environment substrate that is created and maintained by any professional group that claims high status in society. In that sense, medicine should be viewed as no different than law, or even basic science itself. ((Denis G. Rancourt. On the False Science of a Fundamental Basis for Progress”, Activist Teacher, January 5, 2011))

Some prominent critics have made this observation from within the medical establishment, in different ways. For example, the “Gold Effect” was described by Professor T. Gold in 1979 and is the phenomenon in which a scientific (often medical) idea is developed to the status of an accepted position within a professional body or association by the social process itself of scientific conferences, committees, and consensus building, despite not being supported by conclusive evidence. ((R.A. Lyttleton. The Gold Effect. In: Lying Truths. A critical scrutiny of current beliefs and conventions. Duncan R., Weston-Smith M., Eds. Pergamon Press, Oxford, 1979, pp. 182-198))

The “Gold Effect” was reviewed by Drs. Petr Skrabanek and James McCormick in their book Follies and Fallacies in Medicine, ((P. Skrabanek and J. McCormick. Follies and Fallacies in Medicine. Third Edition. Tarragon Press, Whithorn. 1998. pp. 54-55)) and it is used to analyze errors in public health policy and practice, such as the widespread use of cholesterol screening in the prevention of cardiovascular disease. ((A. Hann and S. Peckham. Cholesterol screening and the Gold Effect. Health, Risk & Society, vol. 12, 2010, pp. 33-50. DOI: 10.1080/13698570903499608))

Most published research findings are false

From a different perspective, renowned medical researcher John P.A. Ioannidis applied Bayesian statistical modelling to prove that it is likely that “most published research findings are false”. ((J.P.A. Ioannidis. “Why Most Published Research Findings Are False”, PLoS Medicine, August 2005, vol. 2, issue 8, e124, pages 696-701)) I know something about Bayesian inference theory. ((For example: L. Dou, R.J.W. Hodgson and D.G. Rancourt.  “Bayesian Inference Theory Applied to Hyperfine Parameter Distribution Extraction in Mössbauer Spectroscopy”. Nuclear Instruments and Methods in Physics Research B (NIMB), 1995, vol. 100, pages 511-518.)) I found Dr. Ioannidis’ argument to be entirely rigorous. Other Bayesian practitioners were critical of the work, ((S. Goodman and S. Greenland. “Why Most Published Research Findings Are False: Ploblems in the Analysis”. PLoS Medicine, April 2007, vol. 4, issue 4, e165 e168, page 773)) but Ioannidis ably put them in their place. ((J.P.A. Ioannidis. “Why Most Published Research Findings Are False: Author’s Reply to Goodman and Greenland”. PLoS Medicine, June 2007, vol. 4, issue 6, e224 e214 e215, pages 1132-1133.))

Ioannidis showed that published medical claims of net benefits of a treatment (such as a regiment of one or more drugs) or of policy implementation (such as cancer screening or vaccination), based on statistical evaluation of large randomized trials, are most often false. In his words:

Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias.

He also points out what is essentially an alternative statement of the Gold Effect:

… when more teams are involved in a scientific field in chase of statistical significance … The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.

And he clearly describes main sources of researcher bias:

Prejudice may not necessarily have financial roots. Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings. Many otherwise seemingly independent, university-based studies may be conducted for no other reason than to give physicians and researchers qualifications for promotion or tenure. Such nonfinancial conflicts may also lead to distorted reported results and interpretations. Prestigious investigators may suppress via the peer review process the appearance and dissemination of findings that refute their findings, thus condemning their field to perpetuate false dogma. Empirical evidence on expert opinion shows that it is extremely unreliable.

In his most recent critical overview, Ioannidis is merciless in his assessment of the medical research enterprise, even questioning whether fundamental lab-bench science is of any use in advancing medicine for patient benefit. ((J.P.A. Ioannidis. “Is It Possible to Recognize a Major Scientific Discovery?” Journal of the American Medical Association (JAMA), 2015, vol.314, pages 1135-1137.)) In his words:

… a novel model is needed in funding research to avoid the creation of narrow, isolated specialties that only self-perpetuate … For example, human genetics research has received tremendous funding. This money has not been wasted because other activities and high-tech industry have emerged to support the needs of the genetics community. However, few lives have been saved because of accumulated human genetics knowledge to date, and future prospects (eg, extensions to personalized and precision medicine) also are not promising. Similarly, intellectual fascination in neuroscience for many decades has led to few new practical applications …

Medicine is itself a leading cause of death

Part of the context of medical research is not only that most positive findings of benefits of drug regimes are probably false but also that the drugs themselves, in the hands of clinical practitioners, are lethal. Let us explore this lethality.

Prior to 1999, the mainstream medical establishment did not acknowledge that it is itself a leading cause of death in Western countries. For example, typically the best that the profession could maybe muster was to admit that operative mortality depends on hospital patient volume. ((C.B. Begg et al. “Impact of Hospital Volume on Operative Mortality for Major Cancer Surgery”. Journal of the American Medical Association (JAMA), 1998, vol. 280, no. 20, pages 1747-1751)) This is worrisome enough: Patients are more likely to be killed by surgery in hospitals where the surgical teams get relatively less practice. This, in itself, depreciates the myth of meaningful professional certification and safety accreditations, but it is nothing compared to the tectonic release that was about to occur.

In 1999, the Institute of Medicine, a division of the National Academies of Sciences, Engineering, and Medicine (a US non-profit organization), published its Committee on Quality of Health Care in America’s report entitled “To Err Is Human: Building a Safer Health System”. ((L. Kohn, J. Corrigan and M. Donaldson (Eds.). To Err Is Human: Building a Safer Health System, National Academy Press, DC, 1999)) For the first time, an authoritative body put it to the medical professions that they were themselves responsible for staggering numbers of patient deaths.

In the words of Dr. Barbara Starfield, and many others, it is therefore incontrovertible that establishment medicine is the third leading cause of death in industrialized countries, after deaths from heart disease and cancer, ((B. Starfield. “Is US Health Really the Best in the World?”, Journal of the American Medical Association (JAMA), 2000, vol. 284, no. 4, pages 483-485)) which in turn are causes that medicine can do very little about. The next and fourth leading cause of death is cerebrovascular disease and its rate is far below that from medical-induced (iatrogenic) deaths, such that “medical manslaughter” is not about to give up its rank of third leading cause.

Using Dr. Starfield’s best estimates for 2000, between 6% and 8% of US citizens die from medicine rather than any other cause, including both medical-error deaths and non-error medical deaths. ((Using 230,000 to 284,000 deaths per year, a 2000 US population of 282 million, and the average US longevity of 79 years)) One can only conclude that, in addition, the statistics for debilitating iatrogenic harm that does not cause death and has no net benefit would be staggering if they were tabulated.

The medical professions have reacted with the classic cover-up scenario. There is now a vibrant industry of research about “patient safety”, which “studies” the problem and makes all kinds of policy evaluations and recommendations, without any substantive changes in actual clinical training and practice, and without any resulting measurable improvements. The professional associations are strong at lobbying for ineffective lifestyle recommendations but are virtually silent on asking government to pass laws to require the reporting and investigation of medical errors, never mind iatrogenic non-error deaths and injury.

One might have expected that “To Err is Human” would have jolted medical practitioners into rigorously taking professional responsibility for their actions. But that was not the case. In just one example of a recent study, Li et al. studied all the English-language syndicated media reports about medical errors in cancer “care” published between 2000 (after “To Err is Human”) to 2011. ((J.W. Li et al. “Perceptions of Medical Errors in cancer Care: An Analysis of How the News Media Describe Sentinel Events”, Journal of Patient Safety, vol. 11, no. 1, March 2015, pages 42-51)) They found 64 media reports of egregious errors, with news titles such as:

  • “Montclair surgeon hit with lawsuit; allegedly left gauze in cancer patient”
  • “Surgeon faces discipline for removing wrong breast”
  • “Hospital kept breast cancer surgery blunder secret from me for nine years”
  • “Missing Instruments”
  • “Officer compensated for misdiagnosis: Told she had cancer, she had operations, cashed in savings”
  • “Police arrest doctors who gave teenager fatal injection”
  • “Medical errors killing thousands in Canada”
  • “Tears of the wife who lost a breast by mistake; Mother sues a hospital over its cancer test blunders”
  • “Neglect verdict over hospital overdose: Inquest on cancer victim told of drug error”
  • “Surgeon laughed as he told memy breast had been removed in error”
  • “Doctor admits manslaughter in cancer case”
  • “Clinic overly irradiated 111 patients”
  • “W’chester Hosp Cuts Out Wrong Kidney”
  • “Cancer patient has the wrong kidney taken out by surgeon”
  • “Removal of healthy kidney focus of Tennessee lawsuit”
  • “The women sentenced to die by arrogance; Breast cancer patients failed by health chiefs who ignored warnings over blundering doctor”
  • “Man died after lung removed by mistake”
  • “MD suspended for surgery on the wrong lung. Error, cover-up came in 2000”
  • “LA hospital: Error caused 206 radiation overdoses”
  • “20 People a year incorrectly given chemotherapy, N.L. Health group says”

These are solely the cases that made it into the media. The authors complained that “Four in 10 articles failed to present medical errors as ‘systems’ problems”. The study found four reported types of medical errors: errors implicating medications (34%), diagnoses (25%), radiation (22%), and surgery (19%). However, the study also found that none of the US articles reported medication or diagnosis errors, whereas these were common elsewhere. These differences give an indication of the incompleteness and bias of such media reports.

Despite the medical establishment’s inertia in addressing the small problem that it is the third leading cause of death and that it can’t help with the other leading causes of death, more and more prominent researchers are making the said small problem painfully apparent. One eminent example is the tireless work of Professor Dr. Peter C. Gøtzsche, Nordic Cochrane Centre, Denmark. He has come to the point of flatly concluding that long term use of psychiatric drugs cause more harm than good. In his words, based on a decade of research: ((P.C. Gøtzsche, A.H. Young, J. Crace. “Does long term use of psychiatric drugs cause more harm than good?”, British Medical Journal (BMJ), 12 May 2015, vol. 350, h2435, pages 1-3. doi: 10.1136/bmj.h2435; and see P.C. Gøtzsche. “Author’s reply to Tovey and colleagues”, British Medical Journal (BMJ), 2 June 2015, vol. 350, h2955, page 1. doi: 10.1136/bmj.h2955))

Psychiatric drugs are responsible for the deaths of more than half a million people aged 65 and older each year in the Western world, as I show below. Their benefits would need to be colossal to justify this, but they are minimal. … Overstated benefits and understated deaths …

The American psychiatrist Dr. Peter Breggin is also an outspoken critic of his field of medicine. His legal successes, books and public lectures should give even the most hardened careerist pause. ((Psychiatric Drug Facts with Dr. Peter Breggin))

It’s the brain, stupid

I end Part-I with another important fact that is overlooked or wilfully ignored by the medical establishment. In addition to most published medical research being false, and to medicine being itself the third leading cause of death in the Western world, now this: Stress, as mediated by the brain, is the dominant determinant of individual health, far outweighing any other factor.

The dominant determinant of individual health in primates (including humans) and other mammals is the individual’s rank in the social hierarchy, because rank determines the stress level to which the individual is generally subjected. This is the result of a large body of work, which was reviewed by Robert M. Sapolsky in 2005. ((R.M. Sapolsky. “The Influence of Social Hierarchy on Primate Health”, Science, 29 April 2005, vol. 308, pages 648-652))

Medical students are superficially given lip service about the importance of psychological factors in health, but are trained to ignore anything but lab results, and measurable symptoms.

Nonetheless, stress (both excessive stress and deleterious absence of stress or stimulation) is the overriding determinant of health, via its massive impact on the entire organism. Sapolsky’s most recent commentary is a brilliant overview of the situation. ((R.M. Sapolsky. “Stress and the brain: individual variability and the inverted-U”, Nature Neuroscience, October 2015, vol. 18, no. 10, pages 1344-1346)) In his words:

It is a truism that the brain influences the body and that peripheral physiology influences the brain. Never is this clearer than during stress, where the subtlest emotions or the most abstract thoughts can initiate stress responses, with consequences throughout the body, and the endocrine transducers of stress alter cognition, affect and behavior. … the brain is an endocrine gland, secreting releasing and inhibiting hormones into the hypothalamic-pituitary portal system … the stress response, conceptualized in the context of acute physical crisis, can be robustly activated by purely psychological states, such as loss of control, predictability and social support … prolonged stress increases the odds of being sick. This has facilitated the birth of other subfields (for example, psychoneuroimmunology), and is now an area of tremendous amounts of reductive research. As a result, we have a fairly good idea as to how, say, a fleeting, stressful thought changes transcriptional events relevant to oxidative metabolism in your big toe. … when we are stressed, we learn more readily to be afraid when there is no need to and less readily detect when we are safe. The road to a crippling anxiety disorder is paved with perky amygdaloid synapses. … These linkages both take the form of early life stress predisposing toward adult illness and periods of acute stress during adulthood triggering episodes of disease. … stress is the poster child for the environment part of gene × environment interactions … Is stress more about the unpleasantry in the outside world (that is, the stressor) or the resulting changes in the body (that is, the stress response)? Or is it mostly about the neurobiological and psychological space floating between the two? … the word encompasses all of the above … The far more interesting version of this question addresses the fact that in any species you’d care to study, different individuals respond to stress differently; there are typically dramatic individual differences as to whether a particular event or internal state is even perceived to be stressful. In other words, what is stress…for this individual? Of course, individual variability is not always the case; a severe injury, a major burn or a sprint from a predator will reliably activate the stress response and evoke an aversive subjective sense in virtually any organism. But these are not the circumstances of stress that are most pertinent to understanding health and disease in contemporary life. Instead, individual differences are most notable as we navigate life’s social exigencies. … the response to stress depends on the nature, intensity and duration of a stressor (which at least partially translates into a dependence on the pattern of activation of the sympathetic nervous system, the adrenocortical axis and the other mediators of the stress response).

Sapolsky goes on to describe the unifying concept of the “inverted-U” of stress response:

Enormous unifying clarity came with the recognition that, to a large extent, the effects of stress in the brain form a nonlinear ‘inverted-U’ dose-response curve as a function of stressor severity … with profoundly adverse effects seen in impoverished environments ranging from childhood … to old age, from humans to zoo animals in sterile cages. … And the downswing of the inverted-U is, of course, the universe of “stress is bad for you”.

The physiological and biochemical responses to intense external and perception-mediated stress are massive and involve releases of large arrays of metabolically active agents, on several time scales, and affecting virtually every major body function and body system. ((For example, see: R.M. Sapolsky et al. “How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions”, Endocrine Reviews, vol. 21, no. 1, pages 55-89))

Finally, as part of examining the context of cancer research, we should also be open to even “crazy” ideas from broad areas of social-animal evolution. For example, it is not harmful to consider provocative questions such as: “Does cancer serve a species-survival purpose?” or “Is cancer sometimes an escape strategy for the individual?”.

Just as there is evolutionary adjustment to the systematic use of antibiotics in the medical response to common infections, is cancer adapting as part of an evolutionary response to cancer “treatment”? Are there common circumstances of net advantage for an individual to develop cancer, and be treated for cancer, in terms of escaping a toxic work or family environment? Does stress-induced disease serve the human species? ((For example, see: D.G. Rancourt. A Theory of Chronic Pain: A social and evolutionary theory of human disease and chronic pain. Dissident Voice, December 26, 2011))

Denis G. Rancourt is a former tenured full professor of physics at the University of Ottawa, Canada. He is a researcher for the Ontario Civil Liberties Association. He has published more than 100 articles in leading scientific journals, on physics and environmental science. He is the author of the book Hierarchy and Free Expression in the Fight Against Racism. Denis can be reached at denis.rancourt@gmail.com. Read other articles by Denis.