Cancer's Origin, Prevention, Treatment, and Lifesaving Patient Empowerment and Resilience Strategies

n Friday, December 23, 1971, President Richard Nixon signed the National Cancer Act, which allocated $1.4 billion over three years to fight the "war on cancer," which, at the time, was the second-leading cause of death in the United States.¹ This powerfully evocative Vietnam War--era metaphor suggested that cancer is an insidious adversary to be conquered and subjugated by sheer force. The consequence of this battlefield zeitgeist was that the war was waged with the conventional weapons of surgery and chemotherapy, designed to strike the enemy and decimate its defenses. The war even went nuclear with radiation therapy. But despite a concerted campaign by bureaucratic agencies, academic research institutions, nonprofit organizations, and pharmaceutical corporations, the battle may have been waged blindfolded.

At the 2012 World Oncology Forum held in Lugano, Switzerland, a group of thought leaders from across cancer research and treatment concluded that "enduring disease-free responses are rare, and cures even rarer."² In the journal Frontiers in Oncology, Bryan Oronsky and his colleagues explicitly said that the conventional tools we wield to target treatment-resistant cancer cells inadvertently amplify their power:

Chemotherapy and radiation are the ultimate stress test for cancer cells, leading to an unintended "survival of the fittest" response in which the most sensitive cells are culled from the treatment-resistant herd; inevitably the price of this selection pressure is the emergence of acquired resistance and therapeutic failure, making aggressive therapy a self-defeating process. Nature abhors a vacuum and fills it up with resistant tumor cells, which ultimately dooms the outcome to failure.³

As of 2015, patients worldwide were spending $100 billion per year on cancer treatments, including surgery, chemotherapy, and radiation, while cancer diagnosis rates and deaths from cancer continue to grow unchecked. One quarter of the population still falls prey to an "enemy" that is universally feared but remains poorly understood at a fundamental level.⁴ According to the International Agency for Research on Cancer, in 2012 there were 14.1 million new cancer diagnoses,⁵ and according to the CDC in 2016, cancer was fast approaching heart disease as the number one reason we die.⁶ Toxic and invasive therapies are being used liberally and inappropriately for patients with indolent or slow-growing diseases such as chronic lymphocytic leukemia, follicular low-grade non-Hodgkin lymphoma, and prostate cancer,⁷ as well as for solid cancers (abnormal masses of tissue that usually do not contain cysts or liquid areas), for which there is no empirically demonstrated benefit to either survival or quality of life from using maximum tolerated doses.⁸

The language we use to describe cancer often creates the impression that it is a predetermined time bomb produced by defective genes. In this model, malignancy represents a cell gone rogue due to the accumulation of point mutations--where one nucleotide is substituted for another in a gene sequence--in the genes controlling the cell cycle and proliferation. As a result, we have characterized tens of thousands of candidate genetic alterations in tumor cells, premised upon the assumption that identification of the cancer genome will lead to a suite of targeted therapies and a comprehensive elucidation of cancer biology.⁹ The tenet we have been led to believe is this: if we can isolate the genes responsible, we can find a cure.

While exposure to mutagenic substances contributes to the initiation and promotion of cancer, it is not a complete explanation for the origin of neoplasms. There is much more to cancer than the pat story of our arbitrary genetic inheritance or mutation events putting us on a collision course with death. Yet this model has led cancer patients to abdicate their autonomy and leaves them with the impression that they are merely bystanders in an arms race waged between their cancer cells and the tools at the disposal of their oncologists. Cancer patients then may surrender their fate to medical professionals without even considering alternatives, including proven, lifesaving, and life-enhancing holistic approaches.

It's time to reframe our approach to the challenge of cancer. The all-or-nothing extremism of the medical monolith must be removed in favor of a more nuanced perspective on oncogenesis. In this newfound paradigm, cancer should be regarded as a dynamic process, a spectrum of deviation from the norm, and an adaptive response to a radically divergent environment from the one in which we evolved.

Fear Fuels Cancer

We can't talk about cancer without talking about fear. The fear surrounding cancer has burrowed itself into the deepest recesses and darkest crevices of our being and extinguished all hope. This primal fear has become the lens through which we envision cancer, coloring and clouding our judgment. It has latched on to our fight-or-flight psychology and activated our most primal, black-and-white thinking. Cancer is the aggressor. Fear is the reason we believe we have to fight for our lives and engage in outright war with our own bodies.

This expectation of deadly effects on our physiology, then, becomes a self-fulfilling prophecy. Research published in the journal Cancer Genetics and Cytogenetics has found that cancer cells express receptors for adrenaline known as adrenergic receptors, which respond to the outpouring of catecholamine hormones--dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline)--that occurs with psychological stress. The ensuing hormonal release leads to the poor response of tumors to chemotherapy and is also considered a risk factor for poor prognosis. For example, in patients with colorectal cancer, adrenaline leads to increased expression of an oncogene called ABCB1, which encodes P-glycoprotein.¹⁰ P-glycoprotein transports xenobiotic (foreign) substances, including chemotherapy drugs, out of the cell through efflux pumps, thereby shielding cancer cells from the anticancer effects of conventional treatments. The effects of stress are also associated with increased activity in the mitogen-activated protein kinase (MAPK) pathway, a cascade that increases cancer cell survival, dissemination, and resistance to drug therapy.¹¹ Stress, then, through the synchronous release of multiple hormones, amplifies the cancer process.

The allopathic model, with its misplaced emphasis on "objective" signs and verifiable biomarkers at the expense of patient beliefs, perceptions, and attitudes, is another relic of metaphysician René Descartes, who severed body from mind in his philosophy of dualism five centuries ago. The legacy of the "ghost in the machine" can be found in the mind-set of a cancer patient, which has been shown to affect prognosis within conventional oncology. A prospective, longitudinal study conducted jointly in Malaysia and Boston found that one-fifth of recently diagnosed cancer patients develop post-traumatic stress disorder (PTSD), and more than one-third continue to exhibit PTSD symptoms four years later.¹²

Studies have shown that the psychological toll of cancer diagnosis affects the risk of death.¹³ According to nationwide health registries in Sweden, the risk of suicide during the first 12 weeks following cancer diagnosis was elevated 4.8-fold and remained elevated beyond the first year after diagnosis for all cancers, including esophagus, liver, pancreas, and lung. The study found that cancer patients were 5.6 times more likely to die from heart-related causes, such as heart attack, in the days after receiving a positive cancer diagnosis--not from the cancer but from the heartbreak and devastation wrought by the news. Furthermore, the increased rate of suicide following cancer diagnosis was particularly prominent in those diagnosed with highly fatal cancers, cementing the power of the iatrogenic effect of disease labels.¹⁴ That the divinations of the doctor have the power to predict a person's imminent demise shows us how the words and rituals of Western medicine create potentially harmful power dynamics between physician and patient.

 At a cellular level, the terror that accompanies the cancer diagnosis can drive the pathogenesis of cancer, both precipitating and perpetuating the disease process. Within this view, it is possible that our culturally conditioned beliefs about our vulnerability to cancer sow the seeds of symptoms that are ultimately diagnosed as disease. The antidote requires reframing the lived experience of illness in a new light, bringing curiosity to the conditions the body is seeking and those that it is crying out for you to transform. In order to reverse any illness, we must figure out what the body is demanding through the symptoms it is expressing. Shedding the fear and psychic conflicts underpinning cancer will help to carve out space for its spontaneous resolution.

Overdiagnosis: The Problem with Early Screenings

When we consider the inexactitude of cancer diagnoses and prognoses, the effect of the psychology of fear is especially tragic. The truth is that the most common cancers, such as those of the breast, prostate, and thyroid, have been massively overdiagnosed and overtreated.

This trend of overdiagnosis is confirmed by data from the Journal of the American Medical Association (JAMA) showing significant increases in incidence of early-stage disease without proportional declines in incidence of later-stage disease,¹⁵ alongside statistics showing a rapid rise in cancer diagnosis in the absence of an accompanying rise in death from cancer.¹⁶ Patients may have "the disease," but it may never cause symptoms or death during their expected lifetimes. If cancer were truly being caught earlier, we would expect to see a decline in both later-stage cancer and cancer mortality. These findings suggest that widespread cancer screening has led to detection of "incidentalomas," false positives, and overdiagnosis, which, according to researchers in the British Medical Journal, may wholly offset any disease-specific advantages of screening.¹⁷

In cancer overdiagnosis, we find normal human variations and pathologize these variants as disease. Data published in the Journal of the National Cancer Institute indicates that computerized tomography (CT) colonography scans find abnormalities outside the colon in up to half of examinations.¹⁸ It also reveals that when chest x-ray or mucus samples are used to screen for lung cancer, overdiagnosis occurs 51 percent of the time. In addition, an analysis of 12 randomized trials of cancer screening concluded that overall mortality was unchanged or increased in comparison to unscreened populations in the majority of studies.¹⁹ Another systematic review found that only one-third of screening trials produced reductions in disease-specific mortality, and yet none of the studies exhibited reductions in overall mortality.²⁰ While cancer screening measures have been touted as lifesaving interventions, a sober cost-benefit analysis raises serious concerns.

Despite public confidence in x-ray mammography, a Cochrane Review of mammography following over 600,000 women concluded that there is no definitive mortality benefit with mammographic screening procedures.²¹ This is significant because the Cochrane Collaboration is a relatively independent and unbiased panel of experts with minimal industry affiliations that reviews the strongest evidence available from the medical literature about health care interventions. The International Journal of Epidemiology reports that a high proportion of women have been shown to overestimate the benefits from screening mammography.²² Even when true cancers are detected, any disease-specific mortality reductions may be wholly negated by deaths due to the downstream harms of screening and the effects of overdiagnosis.²³ That such a cavernous divide exists between the efficacy of mammography and public perception is a testament to the lack of informed consent around the procedure.

Cancer screening can beget identification of nonprogressing cancers or occult tumors that may never have threatened the life of the person who harbors them. For example, the cancer might be inherently nonaggressive, or the cellular abnormalities might either fail to progress or naturally regress. Or perhaps the immune system might contain the cancer, or the cancer may outgrow its own blood supply and succumb to starvation.²⁴ In one study, 14 percent of diagnosed solid renal tumors regressed on their own,²⁵ and adenomatous polyps and cervical dysplasia, the precursor lesions of colorectal cancer and cervical cancer, respectively, oftentimes reversed with no treatment at all.²⁶ Even neuroblastoma, a rare childhood cancer, was shown to regress in all 11 subjects who took a watchful waiting strategy in a small trial.²⁷ Prostate cancer overdiagnosis is also common, constituting 60 percent to 67 percent of prostate cancer diagnoses. Further, the tripling of melanoma rates in the context of a generally stable death rate illustrates that most of the increase in melanoma diagnosis is emblematic of overdiagnosis.²⁸

In 2013, a National Cancer Institute--commissioned expert panel published a report in JAMA that concluded that millions of individuals who were diagnosed with cancer and treated aggressively with chemotherapy, radiation, and surgery as a result actually did not have cancer after all. These patients underwent preventive cancer screening programs to "find cancer early." The results revealed tissue abnormalities or lesions that, while misidentified as "cancer" or "precancer" in the past, are now known to have been benign, representing little to no threat to health. This report confirmed what many leading-edge researchers have been saying for years: that millions of people have been wrongly diagnosed with early cancer of the breast, prostate, thyroid, and lung through screening programs--underscoring that campaigns for universal screening recommendations may do more harm than good. The working group of the National Cancer Institute announced that what had been--and still often is--labeled as "cancer" should really be termed "indolent or benign growths of epithelial origin,"²⁹ meaning that these "cancers" often represent harmless morphological variations that often regress on their own without intervention.

As a team of scientists has pointed out in the American Journal of Epidemiology, statistics about the success of screening can be warped by lead time and length bias, concepts that are still familiar mostly to medical experts.³⁰ Lead time is the difference between when a variation is detected "early" by a screening and the moment when it would present with symptoms and be detected through other methods, such as a breast exam. This lead time generates the statistical illusion that the screening program extends survival time, but the reality is that screening merely moves up the date of diagnosis. Length bias, in contrast, refers to the fact that screening-detected cancers tend to be the ones that grow the most slowly. These indolent cancers create few if any symptoms, and they may never progress to harm if left undiagnosed and untreated. In the realm of clinically significant findings, fast-growing tumors (i.e., life-threatening cancers) are of the greatest concern, yet these are precisely the ones that are the most difficult to detect early. It's a recipe for misplaced trust: screening tools can find the growths that don't become aggressive cancer, but they are less likely to find the ones that will. The result is overdiagnosis and overtreatment on an astounding scale.

The phenomenon of overdiagnosis is compounded by the propensity of the medical specialties, compartmentalized into their respective silos, to view the patient through the myopic lenses and constructs of their reductionistic training. Just as everything looks like a nail if all you have is a hammer, everything looks like cancer to a radiologist whose explicit expertise is to search for anomalies. This profound shift in priorities from understanding and treating a patient's subjective, first-hand, experiential complaints to screening and, through diagnostic parameters, finding diseases that often present with no symptoms at all is at the heart of the problem today. Cancer treatment, which was once focused on alleviating the patient's suffering, has become a juggernaut-like force creating arbitrarily circumscribed disease entities and increasingly invasive treatments, often in symptomless patients, which may result in more harm than good in those it claims to serve. The following represent some of the cancers that are most often overdiagnosed.

Breast Cancer

The holy grail of the breast cancer industry, mammography has been the primary instrument in the conventional toolbox for more than three decades. Sixty-eight percent of women believe that mammography will slash breast cancer risk, and 62 percent believe that mammography will cut the risk of breast cancer in half.³¹ Research, however, points to more complex answers. The Swiss medical board, for instance, has based their decision to no longer recommend mammography on research that showed that only one breast cancer death is averted for every 1,000 women screened.³² Another set of statistics, as published in the New England Journal of Medicine (NEJM), show that without breast cancer screening, 5 out of 1,000 women die from breast cancer, whereas 4 out of 1,000 women died from breast cancer for every 1,000 screened. That is, for every 1,000 women who undergo screening, one breast cancer death is averted, but non-breast-cancer deaths may either remain at 39 or increase to 40. In other words, all 1,000 women are at increased risk of exposure to mammography radiation and overdiagnosis, and even if one woman's life is saved from breast cancer, it is possible that one in addition will die from a non-breast-cancer-related death from the screening, canceling any net positive effect. Women may essentially, then, "simply be trading one type of death for another, at the cost of serious morbidity, anxiety, and expense."³³

According to NEJM, over the last 30 years, an estimated 1.3 million people were wrongly diagnosed with breast cancer. In 2008 alone, researchers Archie Bleyer and H. Gilbert Welch approximate that 31 percent of all diagnosed breast cancers represented overdiagnosis.³⁴

Bleyer and Welch argue that mammography has failed as a screening tool, having not met the first prerequisite for a screening modality to reduce cancer-specific mortality: a decline in the number of individuals presenting with late-stage cancer. In their study, they underscore that in order to avoid one breast cancer death, "between two and 10 women will be overdiagnosed and treated needlessly for breast cancer," that "between five and 15 women will be told that they have breast cancer earlier than they would otherwise yet have no effect on their prognosis," and "between 200 and 500 women will have at least one 'false alarm' (50--200 will be biopsied)."³⁵ Another study in the Journal of the American Medical Association indicates that 60 percent of women receive a false positive result when they have undergone screening for a decade or longer.³⁶

Especially troubling is the existential and psychological toll in the wake of misdiagnosis, as explored in a study published in the Annals of Family Medicine. False-positive breast cancer diagnoses were consistently associated with negative psychosocial effects, even three years after patients were declared cancer-free, relative to women who never received a cancer diagnosis. The researchers concluded, therefore, that "false-positive findings on screening mammography causes long-term psychosocial harm."³⁷

Ironically, the "low-dose" radiation incurred from mammography itself represents a potent mammary carcinogen, capable of planting the seeds of cancer deep within irradiated tissue. Radiobiological studies demonstrate that risks of radiation-induced breast cancers from mammography x-rays have been significantly underestimated.³⁸ Evidence from BJR, the British journal of radiology, shows that the low-energy x-rays employed in mammographical screenings are four to six times more effective in damaging DNA than high-energy x-rays,³⁹ which underscores that mammography may play a causative role in precipitating the very outcome it is designed to detect.

In their efforts to avert cancer by complying with medical recommendations and undergoing regular mammography, women are being exposed to cancer-generating radiation. Ironically, BRCA1 and BRCA2 gene mutations--the "breast cancer susceptibility genes"--greatly increase the risk of cancer from exposure to radiation because they inhibit the breasts from repairing DNA damage. According to the international GENE-RAD-RISK study, any diagnostic use of radiation before age 30 increases breast cancer risk by 55 percent for carriers of BRCA1 or BRCA2 mutations,⁴⁰ yet those undergoing breast screening are rarely, if ever, told about these risks.

This calls into question the value of using BRCA1 and BRCA2 gene status to determine breast cancer survival prognosis. For instance, it has been found that the rate of mutation carriers within Ashkenazi Jewish women by age 50 born before 1940 was only 24 percent, whereas the rate of those born after 1940 was 67 percent.⁴⁵ This indicates that environmental factors and not genetic ones are driving the breast cancer epidemic. Another review challenging the presumptive link between BRCA status and mathematically calculable disease risk certainty stated, "In contrast to currently held beliefs of some oncologists, current evidence does not support worse breast cancer survival of BRCA1/ 2 mutation carriers in the adjuvant setting."⁴⁶

The linear and deterministic path from gene to trait to disease risk or prognosis is an archaic way of thinking, whereas epigenetics reflects the complexity and nuance behind the etiological origins of breast cancer more than our genes alone can reveal. "Early detection" does not necessarily equate to prevention, and it is important to consider other environmental and dietary factors.

Prostate Cancer

Similar to breast cancer, prostate cancer is subject to the trends of overdetection, overdiagnosis, and overtreatment, even more so than cancers of the breast, cervix, or colorectum.⁴⁷ Screening for prostate-specific antigen (PSA) is the culprit, as it has doubled the likelihood that a man will be diagnosed with prostate cancer in his lifetime.⁴⁸ The incidence of prostate cancer overdiagnosis due to PSA screening has been estimated to be as high as 50 percent in some studies⁴⁹ and up to 67 percent in others, depending on the screening protocol, population characteristics, and study methodology.⁵⁰

Discovered in 1986, the serine protease PSA protein was initially used to monitor prostate cancer progression and was only later adopted as a surrogate marker for prostate cancer, despite evidence that PSA is not independently prognostic or diagnostic of cancers of the prostate. An enzyme secreted by prostatic epithelial cells that contributes to the liquefaction of seminal fluids, PSA can increase with prostate enlargement and metastatic disease, but it is not cancer-specific, as it can also be elevated with benign prostatic hyperplasia, the latter being a noncancerous condition that commonly afflicts older men.⁵¹ There are also reports of PSA-negative aggressive prostate tumors.⁵² Though higher levels can predict the pathological stage, there is no direct correlation between PSA levels and increasing grade or stage of prostate cancer.⁵³ In effect, the clinical utility of PSA lies mainly in its use as an indicator of prostatic volume and as a tool to monitor cancer progression, regression, or recurrence.⁵⁴

Despite these findings, the American Cancer Society and American Urological Association both still recommend offering annual PSA testing to men aged 50 or older and to those younger who are deemed at risk.⁵⁵ This recommendation directly opposes the results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which showed that PSA screening conferred no reduction in prostate cancer mortality at seven years of follow-up.⁵⁶ The European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, on the other hand, demonstrated that screening reduced risk of death from prostate cancer by 20 percent, but at the cost of significant overdiagnosis.⁵⁷ In order to prevent a single prostate cancer death, 48 men would have to be treated unnecessarily,⁵⁸ exemplifying the broader trend of prostate cancer overdiagnosis. Researchers in the Journal of the National Cancer Institute estimate that over 1 million men have been needlessly treated for prostate cancer since 1986.⁵⁹

Prostatic growths often categorized as prostate cancer may occur as an artifact of aging, as revealed by the Arnold Rich autopsy study. Rich found that a substantial proportion of male cadavers aged 50 or older that were autopsied contained clinically insignificant occult carcinomas of the prostate.⁶⁰ These growths, however, also occur in young men. In one 1996 study, 8 percent of healthy men in their 20s who had died from trauma were found to harbor these prostate cancers.⁶¹ This begs the rhetorical questions of Willet Whitmore, M.D.: "Is cure possible? Is cure necessary? Is cure possible only when it is not necessary?"⁶²

Abnormal PSA results are often followed by invasive biopsies, which pose the risk of hemorrhage and infection, as well as needless radical prostatectomies--partial or complete surgical removal of the prostate--which carry a high risk of impotence, alongside the risks of thrombosis, hemorrhage, bowel injury, infection, and incontinence.⁶³ The ERSPC trial also brings into question the validity of the biopsy itself. Of the men who underwent a biopsy due to elevated PSA, 75.9 percent had a false positive result.⁶⁴ Thirty percent of tumors removed via radical prostatectomy, surgical removal of the prostate gland and surrounding tissues, are found to be clinically insignificant.⁶⁵ In almost one-third of cases, then, when radical prostatectomy is undertaken, research has shown there could be a survival benefit from watchful waiting instead.⁶⁶

Indolent prostate cancers may also be treated with androgen blockade therapy, which increases the likelihood of impotence by 267 percent after one year of treatment alongside 500 percent increases in hot flashes and gynecomastia (enlargement of the male breast gland).⁶⁷ Androgen deprivation therapy likewise increases risk of fracture, coronary artery disease, heart attack, diabetes, and sudden cardiac death.⁶⁸ Since endogenous testosterone is an indicator of health in men and inversely related to all-cause mortality, cancer-related deaths, and cardiovascular mortality,⁶⁹ the testosterone suppression therapy that is often prescribed could be adverse to promoting one's longevity.

The widespread screening efforts for prostate cancer have not translated into significant declines in prostate cancer mortality, as illustrated by comparison with figures from the United Kingdom, where widespread PSA screening has not been implemented.⁷⁰ This is further affirmed by the results of the Cochrane Collaboration (2013), which found that "prostate cancer screening did not significantly decrease prostate cancer--specific mortality in a combined meta-analysis of five RCTs."⁷¹ In addition, men diagnosed with prostate cancer have a significantly elevated risk of suicide and myocardial infarction in the year following diagnosis.⁷²

Collectively, this research points to PSA screening as a flawed endeavor. Even Thomas Stamey, M.D., a professor of urology at Stanford who first advocated PSA screening in 1987, stopped recommending PSA screening for prostate cancer as of 2004.⁷³ Because prostate cancer is slow-growing, with only .003 percent of men over the age of 65 dying of the disease,⁷⁴ it can be significantly suppressed or slowed using dietary and nutritional strategies. For example, before undergoing surgical resection of the prostate gland, we can consider removing dietary risk factors for prostate cancer, such as dairy consumption, first.⁷⁵

Other food-as-medicine interventions can also be impactful. Flaxseed supplementation, for instance, reduces prostate cancer proliferation rates after just one month.⁷⁶ Other bioactive phytonutrients obtained from a whole-foods diet rich in fruits and vegetables can also be protective. Soy proteins, as well as zinc, selenium, vitamin E, and various other antioxidants, may serve as natural inhibitors of prostate carcinogenesis and growth.⁷⁷ When a small study of men with biopsy-proven, organ-localized prostate cancer who had refused conventional treatments were treated with prostate-nutritional supplements from plant-based sources alongside a modified Mediterranean diet, 87 percent experienced clinically significant improvements in PSA levels in an average of approximately three years.

Lung Cancer

Another category of highly overdiagnosed cancer is that of the lung, the leading cause of cancer death worldwide. Low-dose helical computed tomography (CT) has been deployed in the realm of lung cancer to catch tumors at early stages, with potentially disastrous consequences for overdiagnosis. Researchers from the National Lung Screening Trial (NLST) randomly assigned 53,454 people at high risk for lung cancer from 33 United States medical centers to undergo three annual screenings with either low-dose CT or single-view posteroanterior chest radiography to explore how low-dose CT reduced lung cancer mortality. As reported in the New England Journal of Medicine, they found "a total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results."⁷⁸

Further analysis showed that the likelihood that any lung cancer, non-small cell lung cancer, or bronchoalveolar lung cancer detected by low-dose CT represented overdiagnosis was 18.5 percent, 22.5 percent, and 78.9 percent, respectively.⁷⁹ This means, overall, approximately one in five people were told they had treatment-necessary cancer when their lesions may never have caused harm or death if left undiagnosed. Given that lung nodules are often found incidentally during x-rays for unrelated issues such as respiratory complaints and that they present asymptomatically (meaning that the patient does not experience symptoms), they fall into the category of an illusory "disease" that exists only via the lens of modern diagnostic technology. Again, an embedded irony is that CT scans rely on highly carcinogenic radiation, administering 200 times more than a chest x-ray per reading, and it has been estimated that about 0.4 percent of all cancers in the United States may be attributable to the radiation from CT scans.⁸⁰

Thyroid Cancer

Thyroid cancer is the fastest-growing cancer, with its rates quadrupling in the past four decades,⁸¹ and it is projected to be the most common cancer by 2030.⁸² Between 1998 and 2012, a doubling in the age-standardized annual incidence of thyroid cancer among women was observed.⁸³ That being said, several studies have highlighted that the increased rates of thyroid cancer diagnoses were limited to the most indolent form of thyroid cancer, the papillary carcinoma subtype, which are clusters of thyroid cells that form into a mass. Furthermore, the epidemic of thyroid cancer diagnosis occurs without a corresponding increase in thyroid cancer deaths, according to researchers in PLOS ONE.⁸⁴

Papillary lesions of indolent course (PLIC), which are often characterized as "thyroid cancers," have been found to potentially be benign morphological variations that "do not evolve to cause metastatic disease or death."⁸⁵ The vast majority of these thyroid cancer diagnoses are small papillary cancers, the most indolent type of thyroid cancer, with a mortality of less than one percent after 20 years of post-surgical follow-up.⁸⁶ Autopsy studies indicate that many of us harbor these thyroid cancers in our thyroid glands.⁸⁷ When discovered as a postmortem finding, scientists have found that these occult papillary carcinomas (OPCs), which arise from normal follicular cells, should be "regarded as a normal finding which should not be treated when incidentally found."⁸⁸

Radiographic investigations for nonthyroid issues, for example, can detect as incidental findings thyroid abnormalities that would have otherwise gone unnoticed.⁸⁹ Other mechanisms of overdiagnosis include opportunistic screening, where the thyroid is examined in asymptomatic patients, and diagnostic cascades, where multiple tests are conducted in the evaluation of nonspecific health complaints.⁹⁰ Aggressive use of thyroid ultrasounds is particularly implicated. For example, although it is not universally recommended, some centers in South Korea conduct routine ultrasonography screening for thyroid cancer in patients undergoing follow-up after breast cancer surgery. As a result, within a 14-year time period, incidence of thyroid cancer diagnosis increased tenfold in South Korea, a rise that is unparalleled worldwide.⁹¹ The most likely explanation for these skyrocketing rates is not from genetic or environmental causes but from overdiagnosis secondary to unprecedented increases in advanced thyroid imaging and systematic exploration of small thyroid nodules.⁹²

Increasingly tragic is the three- to fourfold parallel rise in unnecessary thyroidectomy that has accompanied thyroid cancer overdiagnosis and the lifelong synthetic thyroid hormone replacement that often ensues.⁹³ In Switzerland, researchers estimate that at least one-third of thyroidectomies, surgical procedures that remove all or part of the thyroid gland, may be unnecessarily performed each year as a consequence of thyroid cancer overdiagnosis.⁹⁴ Thyroidectomy is accompanied by risk of the electrolyte imbalance postoperative hypocalcemia, as well as vocal cord injury and the thyroid replacement therapy upon which the thyroidless patient becomes dependent, and it has its own burden of monitoring and treatment.⁹⁵ Moreover, the overdiagnosis of thyroid lesions often leads to unwarranted treatment with radioactive iodine, which puts patients at risk of secondary malignancies.⁹⁶

In 2016, an international panel of doctors did an about-face in reclassifying the encapsulated follicular variant of papillary thyroid carcinoma as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP), removing the word "carcinoma" and effectively acknowledging that these tumors were never cancer after all. The name is a mouthful, but at the heart of the matter is that this revised diagnosis no longer includes the recommendation for aggressive treatment, and it comes with the implication that papillary lesions of the thyroid should not be characterized as lethal cancers. According to JAMA Oncology, this reclassification is estimated to affect over 45,000 patients per year. The change therefore significantly reduced "the psychological burden, medical overtreatment and expense, and other clinical consequences associated with a cancer diagnosis."⁹⁷ Sadly, medical treatment may be slow to reflect these new guidelines, since it takes on average 17 years for research to be translated into clinical practice.⁹⁸

The Problems with Conventional Cancer Treatment

The National Cancer Institute report that sounded the alarm on overdiagnosis was published in 2013, though since then conventional practice of cancer diagnosis, prevention, and treatment has not undergone radical change. The conventional cancer industry continues to promote chemotherapy and radiation, even though they compromise genetic material. Their genotoxicity fits into the prevailing gene mutational theory of the origin of cancer, as we are targeting cancer cells with cancer-causing therapies.

First deployed in 1946, the original chemotherapeutic agents were derived from nitrogen mustard gas, which was originally used in chemical warfare.⁹⁹ By the early 1990s, anticancer drug development had been transformed from a low-budget, government-supported research effort into a high-stakes, multi-billion-dollar industry.¹⁰⁰ Today, the anticancer drug industry accounts for 10.8 percent of the total market share of the pharmaceutical industry, valued at $100 billion.¹⁰¹

Chemotherapy and radiotherapy are a deadly game of roulette, wherein we rely upon these intrinsically carcinogenic treatments to kill tissue lesions, growths, and abnormalities labeled "cancer" faster than they kill us. As in modern warfare, these modalities are indiscriminate in their propensity to inflict harm, and the decision to strike is based upon how much collateral damage is deemed permissible to the "civilian populations" of noncombatant healthy cells. This approach stands in stark juxtaposition to natural, plant-based anticancer compounds and whole plant extracts that are favorable in their selective cytotoxicity, or the ability to target cancer cells while leaving healthy cells intact. For example, graviola, from the seeds of the soursop fruit, is up to 10,000 times more cytotoxic to colon adenocarcinoma cells than the chemo agent Adriamycin, the trade name for doxorubicin, which is also known as the "red devil" because of its color and cardiotoxic side effects. Even though cell culture studies demonstrate that graviola elicits selective anti--prostate cancer, anti--pancreatic cancer,¹⁰² antihepatoma,¹⁰³ and anti--breast cancer activity,¹⁰⁴ there is still a lack of fiscal incentive for further studies. Because the medical-pharmaceutical-industrial complex revolves around control over synthetic, patentable medications, and because natural products cannot be patented, further research on graviola has stalled.

Another fundamentally faulty premise continues to guide the treatment industry: the belief that tumor regression equals survival. The approval of anticancer drugs is contingent upon demonstration of clinical benefit, which is measured by objective measurements of tumor regression, quality of life improvements, and elongation of the time duration until recurrence.¹⁰⁵ These parameters for measuring success, however, have not translated into a significant benefit to life-span and cannot be taken as surrogate markers, or indicators, of survival.¹⁰⁶ The contribution of cytotoxic chemotherapy to survival is minimal, improving five-year survival by only 2.1 percent and 2.3 percent in the United States and Australia, respectively.¹⁰⁷ The simple fact that response to therapy does not necessarily prolong survival has been established by scientific literature and research,¹⁰⁸ leading a study published in the journal Blood to conclude, "Objective clinical responses to treatment often do not even translate into substantial improvements in overall survival."¹⁰⁹

The study notes numerous examples where response and survival do not track together:

Indolent lymphoma patients who achieved complete remissions (i.e., elimination of all detectable disease) with conventional-
dose therapies in the prerituximab era did not experience a survival advantage over similar patients treated with a "watch and wait" approach. In multiple myeloma, neither the magnitude nor the kinetics of clinical response has an impact on survival. Similarly, significant clinical responses in pancreatic and prostate cancer have not translated into survival benefits.¹¹⁰

And then there is tamoxifen, the frontline treatment deployed to treat estrogen receptor alpha (ERα)--positive breast tumors in premenopausal women. By blocking estrogen receptors, tamoxifen prevents estrogen signaling and the expression of genes involved in cell proliferation and survival.¹¹¹ However, the success of this antiestrogen is often short-lived, as described by Viedma-Rodriguez and colleagues in Oncology Reports: "Patients with estrogen receptor-positive breast cancer initially respond to treatment with anti-hormonal agents such as tamoxifen, but remissions are often followed by the acquisition of resistance and, ultimately, disease relapse."¹¹²

Metabolites of tamoxifen elicit cancer-causing genotoxic effects, damaging genetic material¹¹³ due to overproduction of reactive oxygen species (ROS) during metabolic activation of the antiestrogen agent.¹¹⁴ Tamoxifen has been demonstrated to increase incidence of secondary primary malignancies including endometrial cancer,¹¹⁵ as well as stomach cancer¹¹⁶ and colorectal cancer,¹¹⁷ and there are even reports of development of acute myeloid leukemia (AML) following tamoxifen therapy for breast cancer.¹¹⁸ Tamoxifen use, then, may lead breast cancer patients to simply trade one form of cancer for another. So strong is the link between tamoxifen and endometrial cancer that researchers in the International Journal of Cancer call for an immediate long-term evaluation of the risk-benefit ratio of tamoxifen use.¹¹⁹

Not only that, but tamoxifen is associated with a host of adverse side effects, including subjective complaints of memory¹²⁰ and cognitive deficits,¹²¹ nonalcoholic fatty liver disease,¹²² cataracts,¹²³ stroke, and pulmonary embolism.¹²⁴ Tamoxifen was touted as lifesaving after the release of the ATLAS study in The Lancet, but close examination reveals a major conflict of interest from the study's funding by major pharmaceutical industry sources, including AstraZeneca, and a relatively low magnitude of impact, with a 3.9 percent reduction in breast cancer recurrence and a 2.8 percent reduction in breast cancer mortality.¹²⁵ Thus, the purported differences in breast cancer morbidity and survivability in the five-year versus extended tamoxifen treatment group may reflect the differing degrees to which women were subjected to overdiagnosis and overtreatment.

Rather than representing intrinsic therapeutic value in targeting breast cancer cells, tamoxifen may reduce the likelihood of detection and subsequent risk of overdiagnosis. Given the antiestrogen effects of tamoxifen, longer tamoxifen treatment suppresses growth of estrogen-sensitive tissues within the breast, whether benign or malignant, reducing the likelihood of mammography-detectable lesions, benign tumors, or "abnormal findings." Lower mortality, then, could result from avoiding the psychological and physical trauma that would ensue from a treatment that was inappropriate and misapplied in the first place.

The Old Cancer Paradigm

At the heart of the Old Cancer Paradigm are these three words: burn, cut, poison. Framing cancer as an irrational and irrepressible force of destruction presents what seems like the only option: to attack it with highly toxic weaponry and potentially deadly procedures. However, this scorched-earth policy fundamentally decimates the very immune defenses designed to protect against cancer.

The old thinking behind the origin of abnormal tissue growth, including cancer, is dominated by the somatic mutational theory, which is described by an article in the journal BioEssays as a three-legged stool. The first leg is the assumption that cancer happens when a somatic, or body, cell acquires too many genetic mutations of the wrong kind. The second leg posits that healthy cells are normally inactive, abstaining from the ceaseless proliferation observed in all cancers. Finally, the third leg is the belief that cancer is caused by defects in particular genes that control the cell cycle (the process of DNA duplication and cellular division that results in two identical daughter cells), which prevents cells from dying at appointed times. In this paradigm, mutations happen at random through a combination of inherited defects and environmental exposures, though the former cause is far more emphasized than the latter. This emphasis on genetic causes is not an accident; in the mid-20th century, much of the early research focused on a genetic cause to distract from the increasingly indicting signal of harm around commercial cigarettes.

There are several problems with the genetic cancer theory. One glaring deficiency is that many of the proto-oncogenes that are found to contribute to cancer, at least 40 of which have been discovered in our genome thus far, have evolutionary origins that can be traced back eons to earlier rudimentary life forms and were not produced by sheer chance through the chaos of strictly mutational forces. In fact, when functioning correctly, these proto-oncogenes carry out crucial functions, especially in embryogenesis, cellular growth and proliferation, and regenerative processes.

The idea inherent in genetic theory that cancer represents a collection of cells gone rogue--"a mosaic of mutant cells [that] compete for space and resources"¹²⁶--flies in the face of modern cancer biology, failing to account for the extent of cooperation among cancer cells.¹²⁷ For example, cancer cells collaborate in the processes of angiogenesis and lymphangiogenesis, or the growth of a new vascular network and lymphatic vessels to supply the tumor with nutrients, oxygen, and immune cells and to remove waste products.¹²⁸ Cancer cells likewise exchange chemical mediators with each other and with exogenous tissue, and there is even evidence that less malignant cells can temper the expansion of populations of more malignant cells, restraining and governing their activity.¹²⁹ This phenomenon is best illustrated by the sudden proliferation of metastatic tumors after a primary tumor is surgically resected or by the flourishing of a malignant subpopulation of cells after chemotherapy targets the dominant population of cancer cells.¹³⁰

The "cell gone rogue" theory fails to account for the ability of cancer cells to "deploy a formidable array of survival tricks, sometimes all at once," such as immune system evasion, penetration of the circulatory systems, invasion of organ membranes, colonization of distant body sites, silencing of tumor suppressor genes, and inhibition of cell senescence and apoptosis, the processes by which cells commit suicide or cease to divide, respectively.¹³¹ It also fails to explain how cancer cells generate an arsenal of mitogenic signals and growth factors that prompt cell division, adapt to oxygen-poor and acidic conditions, remove surface-receptor proteins to escape detection by white blood cells, and alter the viscoelastic characteristics of cells to promote tissue infiltration and metastasis (the spreading of cancer cells to other tissues).¹³²

These advantageous traits of cancer cells can be explained by the biomedical paradigm in terms of internal Darwinism, described as a series of fortuitous accidents of evolution where random genetic mutations occur secondary to normal blind Darwinian trial-and-error that, by happenstance, confer a selective advantage to cancer cells, allowing cancer cells to accrue a veritable multifaceted armory that renders them virtually immortal in the face of conventional treatments.¹³³ Researchers Paul Davies, Ph.D., ASU Regents' Professor and Director of the Beyond Center for Fundamental Concepts in Science, and physicist Charles Lineweaver, Ph.D. of the Australian National University poke holes in the internal Darwinism argument by underscoring that random mutations in healthy cells are often detrimental, leading to maladaptation and cell death. It is paradoxical that cancer cells can still thrive with deformed nuclei, gross structural alterations, dramatic chromatin reorganizations, and chaotic karyotypic configurations, including full-blown aneuploidy (the presence of an abnormal number of chromosomes in a cell). There is far more to the story than genetic scrambling producing reprobate cells that forget how to behave.

---

This was an excerpt from chatper 4 of 'Regenerate: Unlocking Your Body's Radical Resilience with the New Biology' an international best-seller published by Hay House, available in 8 languages.

---

References

1. "National Cancer Act of 1971," National Cancer Institute, February 16, 2016, https://www.cancer.gov/about-nci/legislative/history/national-cancer-act-1971.

2. Douglas Hanahan, "Rethinking the War on Cancer," The Lancet 383, no. 9916 (2014): 558--63, https://doi.org/10.1016/S0140-6736(13)62226-6.

3. Bryan Oronsky et al., "The War on Cancer: A Military Perspective," Frontiers in Oncology 4, no. 387 (January 2015): https://doi.org/10.3389/fonc.2014.00387.

4. Kimberly Leonard, "Global Cancer Spending Reaches $100B," U.S. News & World Report, May 5, 2015, https://www.usnews.com/news/blogs/data-mine/2015/05/05/global-cancer-spending-reaches-100b.

5. "Cancer Fact Sheets," Cancer Today, accessed October 14, 2019, http://gco.iarc.fr/today/fact-sheets-cancers?cancer=29&type=0&sex=0.

6. "Leading Causes of Death," CDC/National Center for Health Statistics, last modified March 17, 2017, https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm.

7. Paolo Vineis and Christopher P. Wild, "Global Cancer Patterns: Causes and Prevention," The Lancet 383, no. 9916 (2014): 549--57, https://doi.org/10.1016/S0140-6736(13)62224-2.

8. Ian Haines, "The War on Cancer: Time for a New Terminology," The Lancet 383, no. 9932 (2014): 1883, https://doi.org/10.1016/S0140-6736(14)60907-7.

9. Robert A. Gatenby, Robert J. Gillies, and Joel S. Brown, "Of Cancer and Cave Fish," Nature Reviews Cancer 11, no. 4 (2011): 237--38, https://doi.org/10.1038/nrc3036.

10. Herui Yao et al., "Adrenaline Induces Chemoresistance in HT-29 Colon Adenocarcinoma Cells," Cancer Genetics and Cytogenetics 190, no. 2 (April 15, 2009): 81--87, https://doi.org/10.1016/j.cancergencyto.2008.12.009.

11. Mauricio Burotto et al., "The MAPK Pathway across Different Malignancies: A New Perspective," Cancer 120, no. 22 (November 15, 2014): 3446--56, https://doi.org/10.1002/cncr.28864.

12. Caryn Mei Hsien Chan et al., "Course and Predictors of Post-Traumatic Stress Disorder in a Cohort of Psychologically Distressed Patients with Cancer: A 4-Year Follow-Up Study," Cancer 124, no. 2 (January 15, 2018): 406--16, https://doi.org/10.1002/cncr.30980.

13. Fang Fang et al., "Suicide and Cardiovascular Death after a Cancer Diagnosis," New England Journal of Medicine 366, no. 14 (April 5, 2012): 1310--18, https://doi.org/10.1056/NEJMoa1110307.

14. Fang et al., "Suicide and Cardiovascular Death," 1310--18.

15. Laura J. Esserman, Ian M. Thompson Jr., and Brian Reid, "Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement," JAMA 310, no. 8 (August 28, 2013): 797--98, https://doi.org/10.1001/jama.2013.108415.

16. H. Gilbert Welch and William C. Black, "Overdiagnosis in Cancer," JNCI: Journal of the National Cancer Institute 102, no. 9 (May 5, 2010): 605--13, https://doi.org/10.1093/jnci/djq099.

17. Vinay Prasad, Jeanne Lenzer, and David H. Newman, "Why Cancer Screening Has Never Been Shown to 'Save Lives'--and What We Can Do about It," BMJ 352, no. 8039 (January 6, 2016): h6080, https://doi.org/10.1136/bmj.h6080.

18. Welch, H. Gilbert, and William C. Black, "Overdiagnosis in Cancer." JNCI: Journal of the National Cancer Institute 102, no. 9 (May 5, 2010): 605--13. https://doi.org/10.1093/jnci/djq099.

19. William C. Black, David A. Haggstrom, and H. Gilbert Welch, "All-Cause Mortality in Randomized Trials of Cancer Screening," JNCI: Journal of the National Cancer Institute 94, no. 3 (February 6, 2002): 167--73, https://doi.org/10.1093/jnci/94.3.167.

20. Nazmus Saquib, Juliann Saquib, and John P. A. Ioannidis, "Does Screening for Disease Save Lives in Asymptomatic Adults? Systematic Review of Meta-Analyses and Randomized Trials," International Journal of Epidemiology 44, no. 1 (February 2015): 264--77, https://doi.org/10.1093/ije/dyu140.

21. Peter C. Gøtzsche and Karsten Juhl Jørgensen, "Screening for Breast Cancer with Mammography (Review)," Cochrane Database of Systematic Reviews, no. 6 (2013), https://doi.org/10.1002/14651858.CD001877.pub5.

22. Gianfranco Domenighetti et al., "Women's Perception of the Benefits of Mammography Screening: Population-Based Survey in Four Countries," International Journal of Epidemiology 32, no. 5 (October 2003): 816--21, https://doi.org/10.1093/ije/dyg257.

23. Welch and Black, "Overdiagnosis in Cancer," 605--13.

24. Welch and Black, "Overdiagnosis in Cancer," 605--13.

25. Jingbo Zhang et al., "Distribution of Renal Tumor Growth Rates Determined by Using Serial Volumetric CT Measurements," Radiology 250, no. 1 (January 2009): 137--44, https://doi.org/10.1148/radiol.2501071712.

26. Gloria Y. F. Ho et al., "Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2: Managed by Watchful Waiting," Journal of Lower Genital Tract Disease 15, no. 4 (2011), https://doi.org/10.1097/LGT.0b013e3182216fef.

27. K. Yamamoto et al., "Spontaneous Regression of Localized Neuroblastoma Detected by Mass Screening," Journal of Clinical Oncology 16, no. 4 (April 1998): 1265--69, https://doi.org/10.1200/JCO.1998.16.4.1265.

28. Welch and Black, "Overdiagnosis in Cancer," 605--13 

29. Esserman, Thompson Jr, and Reid, "Overdiagnosis and Overtreatment in Cancer," 797--98.

30. Stephen W. Duffy et al., "Correcting for Lead Time and Length Bias in Estimating the Effect of Screen Detection on Cancer Survival," American Journal of Epidemiology 168, no. 1 (May 25, 2008): 98--104, https://doi.org/10.1093/aje/kwn120.

31. Domenighetti et al., "Women's Perception of the Benefits of Mammography Screening" 816--21.

32. Nikola Biller-Andorno and Peter Jüni, "Abolishing Mammography Screening Programs? A View from the Swiss Medical Board," New England Journal of Medicine 370, no. 21 (April 16, 2014): 1965--67, https://doi.org/10.1056/NEJMp1401875.

33. Prasad, Lenzer, and Newman, "Never Been Shown to 'Save Lives'," h6080. 

34. Archie Bleyer and H. Gilbert Welch, "Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence," New England Journal of Medicine 367, no. 21 (November 21, 2012): 1998--2005, https://doi.org/10.1056/NEJMoa1206809.

35. H. Gilbert Welch and William C. Black. "Overdiagnosis in Cancer." JNCI: Journal of the National Cancer Institute 102, no. 9 (May 5, 2010): 605--13. https://doi.org/10.1093/jnci/djq099.

36. Lydia E. Pace and Nancy L. Keating, "A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions," JAMA 311, no. 13 (April 2, 2014): 1327--35, https://doi.org/10.1001/jama.2014.1398.

37. . John Brodersen and Volkert Dirk Siersma, "Long-Term Psychosocial Consequences of False-Positive Screening Mammography," Annals of Family Medicine 11, no. 2 (March/April 2013): 106--15, https://doi.org/10.1370/afm.1466.

38. G. J. Heyes, A. J. Mill, and M. W. Charles, "Enhanced Biological Effectiveness of Low Energy X-Rays and Implications for the UK Breast Screening Programme," BJR 79, no. 939 (March 2006): 195--200, https://doi.org/10.1259/bjr/21958628.

39. Heyes, Mill, and Charles, "Low Energy X-Rays," 195--200.

40. Anouk Pijpe et al., "Exposure to Diagnostic Radiation and Risk of Breast Cancer among Carriers of BRCA1/2 Mutations: Retrospective Cohort Study (GENE-RAD-RISK)," BMJ (Clinical Research Ed.) 345, no. 7878 (October 13, 2012): e5660, https://doi.org/10.1136/bmj.e5660.

41. Cheryl Lin et al., "The Case against BRCA 1 and 2 Testing," Surgery 149, no. 6 (June 2011): 731--34, https://doi.org/10.1016/j.surg.2010.11.009. 

42. Alexandra J. van den Broek et al., "Worse Breast Cancer Prognosis of BRCA1/BRCA2 Mutation Carriers: What's the Evidence? A Systematic Review with Meta-Analysis," PLOS ONE 10, no. 3 (March 27, 2015): e0120189, https://doi.org/10.1371/journal.pone.0120189.

43. Bleyer and Welch, "Three Decades of Screening Mammography," 1998--2005. 

44. Andrea Veronesi et al., "Familial Breast Cancer: Characteristics and Outcome of BRCA 1--2 Positive and Negative Cases," BMC Cancer 5, no. 70 (2005), https://doi.org/10.1186/1471-2407-5-70.

45. Mary-Claire King, Joan H. Marks, and Jessica B. Mandell, "Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2," Science 302, no. 5645 (October 24, 2003): 643--46, https://doi.org/10.1126/science.1088759. 

46. van den Broek et al., "Worse Breast Cancer Prognosis," e0120189.

47. Fritz H. Schröder et al., "Screening and Prostate-Cancer Mortality in a Randomized European Study," New England Journal of Medicine 360, no. 13 (March 26, 2009): 1320--28, https://doi.org/10.1056/NEJMoa0810084.

48. Esserman, Thompson Jr, and Reid, "Overdiagnosis and Overtreatment in Cancer," 797--98.

49. Gerrit Draisma et al., "Lead Times and Overdetection Due to Prostate-Specific Antigen Screening: Estimates fro m the European Randomized Study of Screening for Prostate Cancer," JNCI: Journal of the National Cancer Institute 95, no. 12 (June 18, 2003): 868--78, https://doi.org/10.1093/jnci/95.12.868. 

50. Stacy Loeb et al., "Overdiagnosis and Overtreatment of Prostate Cancer," European Urology 65, no. 6 (June 2014): 1046--55, https://doi.org/10.1016/j.eururo.2013.12.062.

51. Bridget Bickers and Claire Aukim-Hastie, "New Molecular Biomarkers for the Prognosis and Management of Prostate Cancer--the Post PSA Era," Anticancer Research 29, no. 8 (August 2009): 3289--98, http://ar.iiarjournals.org/content/29/8/3289.abstract.

52. Bickers and Aukim-Hastie, "New Molecular Biomarkers," 3289--98.

53. Shahrokh F. Shariat et al., "Beyond Prostate-Specific Antigen: New Serologic Biomarkers for Improved Diagnosis and Management of Prostate Cancer," Reviews in Urology 6, no. 2 (2004): 58--72, https://www.ncbi.nlm.nih.gov/pubmed/16985579.

54. Bickers and Aukim-Hastie, "New Molecular Biomarkers," 3289--98.

55. Gerald L. Andriole et al., "Mortality Results from a Randomized Prostate-Cancer Screening Trial," New England Journal of Medicine 360, no. 13 (March 26, 2009): 1310--19, https://doi.org/10.1056/NEJMoa0810696.

56. Andriole et al., "Randomized Prostate-Cancer Screening Trial," 1310--19.

57. Schröder et al., "Screening and Prostate-Cancer Mortality," 1320--28.

58. Schröder et al., "Screening and Prostate-Cancer Mortality," 1320--28.

59. Gilbert H. Welch and Peter C. Albertsen. "Prostate Cancer Diagnosis and Treatment after the Introduction of Prostate-Specific Antigen Screening: 1986--2005." Journal of the National Cancer Institute 101, no. 19 (October 7, 2009): 1325--29. https://doi.org/10.1093/jnci/djp278.

60. Arnold Rice Rich, "On the Frequency of Occurrence of Occult Carcinoma of the Prostrate," International Journal of Epidemiology 36, no. 2 (April 2007): 274--77, https://doi.org/10.1093/ije/dym050. 

61. "Stanford Researcher Declares 'PSA Era is Over' in Predicting Prostate Cancer Risk," Stanford Medicine News Center, September 10, 2004, https://med.stanford.edu/news/all-news/2004/stanford-researcher-declares-psa-era-is-over-in-predicting-prostate-cancer-risk.html.

62. Ronald E. Wheeler, "Is It Necessary to Cure Prostate Cancer When It Is Possible? (Understanding the Role of Prostate Inflammation Resolution to Prostate Cancer Evolution)," Clinical Interventions in Aging 2, no. 1 (2007): 153--61, https://www.ncbi.nlm.nih.gov/pubmed/18044088.

.63 Bickers and Aukim-Hastie, "New Molecular Biomarkers," 3289--98.

64. Schröder et al., "Screening and Prostate-Cancer Mortality," 1320--28. 

65. Girish Sardana, Barry Dowell, and Eleftherios P. Diamandis, "Emerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer," Clinical Chemistry 54, no. 12 (December 2008): 1951--60, https://doi.org/10.1373/clinchem.2008.110668.

66. Anna Bill-Axelson et al., "Radical Prostatectomy versus Watchful Waiting in Localized Prostate Cancer: The Scandinavian Prostate Cancer Group-4 Randomized Trial," JNCI: Journal of the National Cancer Institute 100, no. 16 (August 20, 2008): 1144--54, https://doi.org/10.1093/jnci/djn255.

67. Arnold L. Potosky et al., "Quality of Life following Localized Prostate Cancer Treated Initially with Androgen Deprivation Therapy or No Therapy," JNCI: Journal of the National Cancer Institute 94, no. 6 (March 20, 2002): 430--37, https://doi.org/10.1093/jnci/94.6.430.

68. Grace L. Lu-Yao et al., "Survival following Primary Androgen Deprivation Therapy among Men with Localized Prostate Cancer," JAMA 300, no. 2 (July 9, 2008): 173--81, https://doi.org/10.1001/jama.300.2.173.

69. Kay-Tee Khaw et al., "Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men," Circulation 116, no. 23 (December 4, 2007): 2694--701, https://doi.org/10.1161/CIRCULATIONAHA.107.719005.

70. S. E. Oliver, D. Gunnell, and J. L. Donovan, "Comparison of Trends in Prostate-Cancer Mortality in England and Wales and the USA," The Lancet 355, no. 9217 (2000): 1788--89, https://doi.org/10.1016/S0140-6736(00)02269-8.

71. Dragan Ilic et al., "Screening for Prostate Cancer," Cochrane Database of Systematic Reviews, no. 1 (2013): CD004720, https://doi.org/10.1002/14651858.CD004720.pub3.

72. Fang et al., "Suicide and Cardiovascular Death," 1310--18.

73. "PSA Era is Over," Stanford Medicine News Center, 2004.

74. "PSA Era is Over," Stanford Medicine News Center, 2004.

75. E. Kesse et al., "Dairy Products, Calcium and Phosphorus Intake, and the Risk of Prostate Cancer: Results of the French Prospective SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydants) Study," British Journal of Nutrition 95, no. 3 (2006): 539--45, https://doi.org/10.1079/BJN20051670.

76. Wendy Demark-Wahnefried et al., "Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery," Cancer Epidemiology Biomarkers & Prevention 17, no. 12 (December 2008): 3577--87, https://doi.org/10.1158/1055-9965.EPI-08-0008. 

77. Wheeler, "Is It Necessary to Cure Prostate Cancer?," 153--61.

78. Denise R. Aberle et al., "Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening," New England Journal of Medicine 365, no. 5 (August 4, 2011): 395--409, https://doi.org/10.1056/NEJMoa1102873.

79. Edward F. Patz Jr. et al., "Overdiagnosis in Low-Dose Computed Tomography Screening for Lung Cancer," JAMA Internal Medicine 174, no. 2 (February 2014): 269--74, https://doi.org/10.1001/jamainternmed.2013.12738.

80. David Brenner and Eric Hall, "Computed Tomography--An Increasing Source of Radiation Exposure," New England Journal of Medicine 357, 22 (2007): 2277--84, https://www.doi.org/10.1056/NEJMra072149.

81. Juan P. Brito et al., "Papillary Lesions of Indolent Course: Reducing the Overdiagnosis of Indolent Papillary Thyroid Cancer and Unnecessary Treatment," Future Oncology 10, no. 1 (December 11, 2013): 1--4, https://doi.org/10.2217/fon.13.240.

82. Lola Rahib et al., "Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States," Cancer Research 74, no. 11 (June 2014): 2913--21, https://doi.org/10.1158/0008-5472.CAN-14-0155.

83. Sabrina Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer: A Population-Based Temporal Trend Study," PLOS ONE 12, no. 6 (June 14, 2017): e0179387, https://doi.org/10.1371/journal.pone.0179387.

84. Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer," e0179387.

85. Brito et al., "Papillary Lesions of Indolent Course," 1--4.

86. Brito et al., "Papillary Lesions of Indolent Course," 1--4.

87. Brito et al., "Papillary Lesions of Indolent Course," 1--4.

88. H. Rubén Harach, Kaarle O. Franssila, and Veli‐Matti Wasenius, "Occult Papillary Carcinoma of the Thyroid. A 'normal' Finding in Finland. A Systematic Autopsy Study," Cancer 56, no. 3 (August 1985): 531--38, https://doi.org/10.1002/1097-0142(19850801)56:3<531::aid-cncr2820560321>3.0.co;2-3.

89. Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer," e0179387.

90. Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer," e0179387.

91. Sun-Seog Kweon et al., "Thyroid Cancer Is the Most Common Cancer in Women, Based on the Data from Population-Based Cancer Registries, South Korea," Japanese Journal of Clinical Oncology 43, no. 10 (July 25, 2013): 1039--46, https://doi.org/10.1093/jjco/hyt102.

92. Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer," e0179387.

93. Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer," e0179387.

94. Jegerlehner et al., "Overdiagnosis and Overtreatment of Thyroid Cancer," e0179387.

95. Brito et al., "Papillary Lesions of Indolent Course," 1--4. 

96. N. Gopalakrishna Iyer et al., "Rising Incidence of Second Cancers in Patients with Low-Risk (T1N0) Thyroid Cancer Who Receive Radioactive Iodine Therapy," Cancer 117, no. 19 (October 1, 2011): 4439--46, https://doi.org/10.1002/cncr.26070.

97. Yuri E. Nikiforov et al., "Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors," JAMA Oncology 2, no. 8 (August 2016): 1023--29, https://doi.org/10.1001/jamaoncol.2016.0386.

98. Zoë Slote Morris, Steven Wooding, and Jonathan Grant, "The Answer Is 17 Years, What Is the Question: Understanding Time Lags in Translational Research," Journal of the Royal Society of Medicine 104, no. 12 (December 2011): 510--20, https://doi.org/10.1258/jrsm.2011.110180.

99. J. D. Nabarro, "Nitrogen Mustard Therapy in Reticuloses," British Journal of Radiology 24 (1951): 507--10.

100. Tao Wang et al., "Cancer Stem Cell Targeted Therapy: Progress amid Controversies," Oncotarget 6, no. 42 (2015): 44191--206, https://doi.org/10.18632/oncotarget.6176.

101. Wang et al., "Cancer Stem Cell Targeted Therapy," 44191--206.

102. Geum-Soog Kim et al., "Muricoreacin and Murihexocin C, Mono-Tetrahydrofuran Acetogenins, from the Leaves of Annona Muricata in Honour of Professor G. H. Neil Towers 75th Birthday," Phytochemistry 49, no. 2 (1998): 565--71, https://doi.org/10.1016/S0031-9422(98)00172-1.

103. Chih-Chuang Liaw et al., "New Cytotoxic Monotetrahydrofuran Annonaceous Acetogenins from Annona Muricata," Journal of Natural Products 65, no. 4 (April 2002): 470--75, https://doi.org/10.1021/np0105578.

104. Yumin Dai et al., "Selective Growth Inhibition of Human Breast Cancer Cells by Graviola Fruit Extract In Vitro and In Vivo Involving Downregulation of EGFR Expression," Nutrition and Cancer 63, no. 5 (July 2011): 795--801, https://doi.org/10.1080/01635581.2011.563027.

105. Carol Ann Huff et al., "The Paradox of Response and Survival in Cancer Therapeutics," Blood 107, no. 2 (January 15, 2006): 431--34, https://doi.org/10.1182/blood-2005-06-2517.

106. Huff et al., "Paradox of Response and Survival," 431--34.

107. Graeme Morgan, Robyn Ward, and Michael Barton, "The Contribution of Cytotoxic Chemotherapy to 5-Year Survival in Adult Malignancies," Clinical Oncology 16, no. 8 (December 2004): 549--60, https://doi.org/10.1016/j.clon.2004.06.007.

108. U. Abel, "Chemotherapy of Advanced Epithelial Cancer - a Critical Review," Biomedicine & Pharmacotherapy 46, no. 10 (1992): 439--52, https://doi.org/10.1016/0753-3322(92)90002-O.

109. Huff et al., "Paradox of Response and Survival," 431--34.

110. Huff et al., "Paradox of Response and Survival," 431--34.

111. Qin Feng et al., "An Epigenomic Approach to Therapy for Tamoxifen-Resistant Breast Cancer," Cell Research 24, no. 7 (2014): 809--19, https://doi.org/10.1038/cr.2014.71.

112. Rubí Viedma-Rodríguez et al., "Mechanisms Associated with Resistance to Tamoxifen in Estrogen Receptor-Positive Breast Cancer (Review)," Oncology Reports 32, no. 1 (2014): 3--15, https://doi.org/10.3892/or.2014.3190.

113. Dan Yao et al., "Synthesis and Reactivity of Potential Toxic Metabolites of Tamoxifen Analogues: Droloxifene and Toremifene o-Quinones," Chemical Research in Toxicology 14, no. 12 (December 2001): 1643--53, https://doi.org/10.1021/tx010137i.

114. Giovanni Pagano et al., "The Role of Oxidative Stress in Developmental and Reproductive Toxicity of Tamoxifen," Life Sciences 68, no. 15 (2001): 1735--49, https://doi.org/10.1016/S0024-3205(01)00969-9.

115. Bernard Fisher et al., "Endometrial Cancer in Tamoxifen-Treated Breast Cancer Patients: Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14," JNCI: Journal of the National Cancer Institute 86, no. 7 (April 6, 1994): 527--37, https://doi.org/10.1093/jnci/86.7.527.

116. Y. Matsuyama et al., "Second Cancers after Adjuvant Tamoxifen Therapy for Breast Cancer in Japan," Annals of Oncology 11, no. 12 (December 2000): 1537--43, https://doi.org/10.1093/oxfordjournals.annonc.a010406.

117. Lars E. Rutqvist et al., "Adjuvant Tamoxifen Therapy for Early Stage Breast Cancer and Second Primary Malignancies," JNCI: Journal of the National Cancer Institute 87, no. 9 (May 3, 1995): 645--51, https://doi.org/10.1093/jnci/87.9.645.

118. S. Yalçin et al., "Acute Leukaemia during Tamoxifen Therapy," Medical Oncology 14, no. 1 (1997): 61--62, https://doi.org/10.1007/BF02990948.

119. Hervé Mignotte et al., "Iatrogenic Risks of Endometrial Carcinoma after Treatment for Breast Cancer in a Large French Case-Control Study." International Journal of Cancer 76, no. 3 (May 4, 1998): 325--30, https://doi.org/10.1002/(SICI)1097-0215(19980504)76:3<325::AID-IJC7>3.0.CO;2-X.

120. Annlia Paganini-Hill and Linda J. Clark, "Preliminary Assessment of Cognitive Function in Breast Cancer Patients Treated with Tamoxifen," Breast Cancer Research and Treatment 64, no. 2 (November 1, 2000): 165--76, https://doi.org/10.1023/A:1006426132338.

121. Paganini-Hill and Clark, "Preliminary Assessment of Cognitive Function,"165--76.

122. Yoshihisa Nemoto, et al., "Tamoxifen-Induced Nonalcoholic Steatohepatitis in Breast Cancer Patients Treated with Adjuvant Tamoxifen," Internal Medicine 41, no. 5 (2002): 345--50, https://doi.org/10.2169/internalmedicine.41.345.

123. Annlia Paganini-Hill and Linda J Clark, "Eye Problems in Breast Cancer Patients Treated With Tamoxifen." Breast Cancer Research and Treatment 60, no. 2 (March 2000): 167--172, https://doi.org/10.1023/a:1006342300291.

124. Lin, Hsien-Feng Lin et al., "Correlation of the Tamoxifen Use with the Increased Risk of Deep Vein Thrombosis and Pulmonary Embolism in Elderly Women with Breast Cancer: A Case-Control Study," Medicine 97, no. 51 (December 2018): e12842--e12842, https://doi.org/10.1097/MD.0000000000012842.

125. Christina Davies et al., "Long-Term Effects of Continuing Adjuvant Tamoxifen to 10 Years versus Stopping at 5 Years after Diagnosis of Oestrogen Receptor-Positive Breast Cancer: ATLAS, a Randomised Trial," The Lancet 381, no. 9869 (March 9, 2013): 805--16. https://doi.org/10.1016/S0140-6736(12)61963-1.

126. Lauren M. F. Merlo et al., "Cancer as an Evolutionary and Ecological Process," Nature Reviews Cancer 6, no. 12 (2006): 924--35, https://doi.org/10.1038/nrc2013.

127. Paul C. W. Davies and Charles H. Lineweaver, "Cancer Tumors as Metazoa 1.0: Tapping Genes of Ancient Ancestors," Physical Biology 8, no. 1 (February 2011): 15001, https://doi.org/10.1088/1478-3975/8/1/015001.

128. Naoyo Nishida et al., "Angiogenesis in Cancer," Vascular Health and Risk Management 2, no. 3 (2006): 213--19, https://doi.org/10.2147/vhrm.2006.2.3.213.

129. Davies and Lineweaver, "Cancer Tumors as Metazoa 1.0," 15001.

130. Davies and Lineweaver, "Cancer Tumors as Metazoa 1.0," 15001.

131. Davies and Lineweaver, "Cancer Tumors as Metazoa 1.0," 15001.

132. Davies and Lineweaver, "Cancer Tumors as Metazoa 1.0," 15001.

133. Davies and Lineweaver, "Cancer Tumors as Metazoa 1.0," 15001.