Can stress cause cancer

Contents

Psychological Stress and Cancer

People who have cancer may find the physical, emotional, and social effects of the disease to be stressful. Those who attempt to manage their stress with risky behaviors such as smoking or drinking alcohol or who become more sedentary may have a poorer quality of life after cancer treatment. In contrast, people who are able to use effective coping strategies to deal with stress, such as relaxation and stress management techniques, have been shown to have lower levels of depression, anxiety, and symptoms related to the cancer and its treatment. However, there is no evidence that successful management of psychological stress improves cancer survival.

Evidence from experimental studies does suggest that psychological stress can affect a tumor’s ability to grow and spread. For example, some studies have shown that when mice bearing human tumors were kept confined or isolated from other mice—conditions that increase stress—their tumors were more likely to grow and spread (metastasize). In one set of experiments, tumors transplanted into the mammary fat pads of mice had much higher rates of spread to the lungs and lymph nodes if the mice were chronically stressed than if the mice were not stressed. Studies in mice and in human cancer cells grown in the laboratory have found that the stress hormone norepinephrine, part of the body’s fight-or-flight response system, may promote angiogenesis and metastasis.

In another study, women with triple-negative breast cancer who had been treated with neoadjuvant chemotherapy were asked about their use of beta blockers, which are medications that interfere with certain stress hormones, before and during chemotherapy. Women who reported using beta blockers had a better chance of surviving their cancer treatment without a relapse than women who did not report beta blocker use. There was no difference between the groups, however, in terms of overall survival.

Although there is still no strong evidence that stress directly affects cancer outcomes, some data do suggest that patients can develop a sense of helplessness or hopelessness when stress becomes overwhelming. This response is associated with higher rates of death, although the mechanism for this outcome is unclear. It may be that people who feel helpless or hopeless do not seek treatment when they become ill, give up prematurely on or fail to adhere to potentially helpful therapy, engage in risky behaviors such as drug use, or do not maintain a healthy lifestyle, resulting in premature death.

How stress affects cancer risk

Stress is a part of life. You feel it when you’re preparing for the holidays, stuck in traffic or worrying about a friend’s health. While a little stress is nothing to fret about, the kind of intense worry that lingers for weeks or months may make it hard for you to stay healthy.

“Stress has a profound impact on how your body’s systems function,” says Lorenzo Cohen, Ph.D., professor of General Oncology and Behavioral Science, and director of the Integrative Medicine Program at MD Anderson. Health experts are still sorting out whether stress actually causes cancer. Yet there’s little doubt that it promotes the growth and spread of some forms of the disease. Put simply, “stress makes your body more hospitable to cancer,” Cohen says.

Not all stress is equally harmful

There are two different types of stress, and only one seems to be really bad for your health, says Anil K. Sood, M.D., professor of Gynecologic Oncology and Reproductive Medicine at MD Anderson.

Short-term or acute stress, like the type you might feel before giving a speech or fighting holiday shopping crowds, tends to subside as soon as the event passes. “It’s stress that comes from situations you know you can manage or will be over at some set time,” Cohen says.

But long-term or chronic stress is more damaging. That type of stress springs from situations that last many weeks or months with no definite end point. “Caring for a sick loved one or dealing with a long stint of unemployment are common causes of chronic stress,” Cohen says.

This type of no-end-in-sight stress can weaken your immune system, leaving you prone to diseases like cancer. It also ups your risk for digestive problems and depression. “Chronic stress also can help cancer grow and spread in a number of ways,” Sood says.

Stress hormones can inhibit a process called anoikis, which kills diseased cells and prevents them from spreading, Sood says. Chronic stress also increases the production of certain growth factors that increase your blood supply. This can speed the development of cancerous tumors, he adds.

Find healthy ways to manage stress

What can you do about stress? Removing the cause is the clear answer. But that’s not always possible when it comes to the types of things that cause chronic stress, Cohen says.

Even if you can’t rid yourself of the source of your stress, you can learn to manage it. This can help you keep a lid on chronic stress. It also can help you prevent minor sources of stress from lingering to a point where they’re affecting your health. Below, Cohen shares stress-reducing strategies.

Talk to a professional

A psychiatrist or psychologist can teach you healthy ways to manage your stress.

Strategies may include talk therapy and cognitive behavioral therapy (CBT). These can help your brain uncover the connections between your thoughts, emotions and behaviors. “CBT can provide you with mental tools to manage the types of worry and anxiety that screw up your immune system and increase your disease risks,” Cohen says.

Practice meditation or yoga

Mindfulness meditation and yoga have been proven to combat stress. These movement-based activities give your mind a break from stress. They also can improve your mood and quality of life.

Aim for at least two 20-minute periods a day of meditation or similar relaxation techniques, Cohen says. That time shouldn’t include stimulating activities like watching television. “Sit quietly and try to keep your mind off any concerns. Think about visiting your favorite vacation spot or a quiet, safe place like your garden.”

Mediation and yoga also can help your brain soften the links between your thoughts, your emotions and unhealthy biological changes, he says. Put simply, these practices dampen your brain and body’s reactions to stressful events.

Get adequate sleep

“Getting eight hours of sleep each night is a great defense against stress,” Cohen says. Why? A full night of sleep is essential to proper immune function. It also affects your mood, memory and ability to focus, experts say. Sticking to a regular sleep schedule, avoiding TV in bed and exercising regularly can all help you sleep more soundly.

Take stress seriously

It’s important to understand the negative consequences of stress, especially when it comes to your cancer risks. “Chronic stress is not something anyone in our society should take lightly,” Cohen says.

If you feel crankier than usual, you don’t have the energy you once had or you’re sleeping poorly, all of those could be signs of stress, Cohen says. Take steps to fix your problem before it affects your health in more serious ways.

Request an appointment at MD Anderson’s Lyda Hill Cancer Prevention Center online or call 877-632-6789.

The Role of Psychological Factors in Cancer Incidence and Prognosis

Introduction

This article reviews the literature regarding the possible effects of various psychological factors on cancer incidence and prognosis. For a clear understanding of the findings in the literature, a number of terms need to be defined. The term “psychological factors” refers to personality or behavior traits or reactions. In studies of psychological factors and cancer, these are the independent variables, with one restriction: If a psychological factor is associated with a physical carcinogen, it will not be considered an acceptable independent variable, although it may be regarded as a possible confounder. For example, it is claimed that certain traits predispose a person to smoking. Those traits will not be of interest insofar as they affect smoking and its carcinogenic consequences, but only insofar as they may affect cancer independently of smoking.

The dependent variables are cancer incidence, mortality, and prognosis (disease-free interval and survival time). Possible confounders, cofactors, or primary etiologic agents that may act in conjunction with psychological factors include familiar factors such as radiation, genetic attributes, viruses, smoking, and exposure to chemicals, as well as some less familiar factors.

Incidence of cancer is determined in two ways, either by clinical diagnosis or at autopsy. In both cases, the malignancy has had to grow to the point of detection. That is, if it is a blood or lymphatic cancer, enough cells have been transformed to be detected, and if a solid tumor, it has grown large enough to be detected by x-ray, palpation, sonogram, visualization, or some other method. The first actual mutation of a cell to malignancy, however, has taken place long before-in rare cases months before, and in most cases years before . For example, the median time to detection of leukemia incidence after the atomic bomb was dropped on Hiroshima was between 6 and 7 years . The estimated median growth time to detection for breast cancer is 7 to 11 years, depending on the researchers . According to Steel , in a mix of several cancers, with lung heavily represented, the median was about 5.5 years. Thus, all incidence statistics are a combination of the first mutation of a cell to cancer and the progression of that cancer to detectable size.

Another issue is type of study. The two classic types of epidemiologic studies are case-control, sometimes called retrospective, and cohort, sometimes called prospective. In case-control studies, a group of cancer patients, cancer survivors, or patients with recurrence is selected, together with a control group, and the researcher measures some putatively discriminating attribute in both groups to see whether they differ in respect to that attribute.

In cohort studies, an attribute is measured in all members of the cohort before the outcome of disease, death, or recurrence, and the researcher waits to see who gets cancer or not, survives or not, or suffers a recurrence or not. The pair of groups being tested is examined for differences in outcome that may have emerged, given the existence of differences in the attributes originally measured. For example, if the pair of groups in the population is defined as “those who are stressed” and “those not stressed,” the risk factor is the condition of being stressed, and the control condition is not being stressed. The proportion who get cancer during the given follow-up period in the group with the risk factor is compared with the proportion who get cancer during this period in the group without the risk factor.

This distinction between types of study is important, because the case-control type, when used only on a sample and not the population, is subject to a number of possible biases. Such potential biases make it difficult to decide which case-control studies to accept, doubt, or reject. Cohort studies, which are also subject to some biases, but not nearly so many or so damaging as those characterizing many case-control studies, are more trustworthy and involve less risk of a false conclusion.

The Variety of Psychosocial Factors

A variety of psychosocial factors have been used as independent variables in the past. These include not only directly measured variables but also those inferred from results on an instrument that provides an indirect measure (eg, the Rorschach test). In most case-control studies, the authors imply that because they found a relationship, the factor existed before the tumor was discovered, and they seldom remark on whether it existed before malignant transformation. The analyst is left hanging in the air because the researchers had not learned enough about the disease to know the meaning or implication of their finding.

The Table lists a number of psychosocial factors (with the most important items discussed below). Each of them has been examined at least once as a risk factor in some study in the literature (see Fox for a bibliography). Very few mention the possibility that the factor, eg, depression or suppression of emotions, may have arisen from the biologic effects of the cancer itself or from the patient’s knowledge that he or she had the disease. Personally, I do not think that such a possibility was ignored; I think the possibility never even occurred to the researchers in the first place because of their narrow disciplinary focus. Most of those researchers were psychologists or psychiatrists, although a few were somatic physicians, eg, Kissen and Thomas .

More recently, both psychologists and psychiatrists have become more aware of the need to examine the effects of cancer on the psyche, as well as the potential interference by a number of possible confounders, both demographic and biologic, with proper research methods. Nonetheless, such confounders still receive limited attention.

Stress

Stress will be defined here as the psychic and physiologic disequilibrium caused by some event, which will be called a stressor.

Stress in Animals

The earliest work on the effect of psychological factors on cancer dealt mainly with humans. But soon afterwards, a number of studies appeared in which the relationship of stress and cancer in animals was explored. Important early work on this topic was done by Riley , who carried out extensive studies on the topic, and Seifter et al . They and others who followed found clear evidence that stress in rodents led to faster growth of transplanted tumors or those caused by injection of oncogenic viruses, and shorter survival times than in nonstressed control animals. This was also true for development and growth of spontaneous tumors. It is of note that Riley’s early work on spontaneous tumors was done in animals with virus-infected milk, like the mammary tumors caused by the Bittner virus.

On the other hand, some researchers, eg, Newberry and Sengbusch , found stress to inhibit tumor development and growth in animals under some conditions. In a thorough review of these and other findings, Justice presented an extensive list of variables that stimulate and inhibit tumor development. The most important inference he drew, now well confirmed, was that viral tumors in animals are adversely affected by stress, while those induced by chemical carcinogens are favorably influenced by stress.

In view of the role attributed to the immune system in protecting against cancer growth and possibly initiation, one might be tempted to transfer these animal findings to humans. Yet several facts suggest caution.

1. Humans, guinea pigs, and certain other animals are considerably less sensitive to corticosteroid proliferation than the major rodent species used in the laboratory, and, indeed, even among these rodent species, various strains differ in their sensitivity to glucocorticoids. Thus, the major finding of Riley , Seifter , and others that stress-induced high glucocorticoid levels in rodents led to increased tumor growth might not be duplicated in humans, even if human cortisol levels did rise with stress.

2. Humans are outbred, with a variety of responses to many physiologic stimuli; mice and rats used in laboratories historically have been inbred to produce cancer-prone strains. While there are now more varied strains, overall that history cannot be ignored.

3. Tumor transplants or heavy doses of carcinogens introduce strong antigens, that is, stimuli to immune recognition and response, with consequent greater protection against the tumor. Spontaneous human tumors take a long time to develop and probably involve relatively weak or even absent antigen proliferation, and hence limited or even absent immune recognition of and response to antigens.

4. When animals are immunosuppressed, they develop tumors in excess of normal at many sites, each strain being susceptible to tumors at the site peculiar to that strain, eg, liver, lung, testes. When humans are immunosuppressed, they also develop tumors in excess of normal, but most frequently lymphoreticular tumors; that is, the focus of the immunosuppressive stimulus is the immune system itself. The incidence of reticulum cell sarcoma in immunosuppressed individuals, for example, is 150 times that of the population, whereas the incidence of other tumors (except other lymphomas, which is also very high) is about twice that of the population.

5. Justice reported that stress inhibited growth in chemically induced animal tumors. While many stress experiments in animals involve viral tumors, with associated stimulation of tumor growth, in humans, the proportion of viral tumors is small, on the order of 3% to 4% of all tumors.

Thus, if one extrapolated directly and incautiously to humans from animal findings, one would conclude that overall, stress is a depressant of tumor development and growth, as found by Newberry and others in animals, rather than a stimulant to tumor growth, as many researchers suggest. For a number of reasons, such a conclusion should not be drawn. Although the animal findings are important, they should form the bases for hypotheses, not conclusions, about the effects of stress on human cancers.

Human Stress

This discussion will focus on cohort studies, as there are several reasons for giving little emphasis to case-control studies. First, cancer can and does produce physical, psychological, and attitudinal changes, mostly negative, that can bias conclusions . Second, these changes in patients are known to increase reports of stressful events when compared with controls .

Third, and perhaps most important, one can never be sure that the patient group sample is unbiased, and that the control group is matched to the patient group in regard to variables that might lead to erroneous conclusions. A very limited list of such variables would include the tumor’s site, stage, histologic grade, depth of invasion, and size; the degree of lymphocytic invasion at the tumor site; the degree of microvascularization; the patient’s age, sex, socioeconomic level, race, smoking status, prior tumor history, alcohol habits, body mass index, status of certain genes (eg, p53), compliance with treatment regimen, and, for breast cancer, age at menarche, age at menopause, oral contraceptive use, estrogen-receptor level, and menstrual stage at operation. In a large cohort study, one hopes that the sheer size of the sample will cause most of these variables to even out among the groups with and without the risk factor.

Case-Control Studies–Several early workers, using the case-control model, reported a greater number of stressful events occurring earlier in life in patients with cancer than in the noncancer groups, eg, Greene , and LeShan and Worthington . But most later case-control studies showed no excess of traumatic events among patients, eg, Schonfield and Greer (a short review of his studies).

Among the more recent case-control studies, we find similar contradictory results. Ramirez et al compared frequency of traumatic events between diagnosis of breast cancer and first recurrence among 50 patients with recurrence with the frequency of such events during a similar period in 50 patients without recurrence. They found an excess of reported stressful events among those patients with recurrence.

In contrast, Priestman et al , who studied 300 women, 100 with malignancy, 100 with benign tumors, and 100 controls, found that the severity and nature of the stressors did not differ among the groups. In fact, the controls experienced more stressful events than did the benign group, and the benign group experienced more than those with cancer.

Early Cohort Studies–The earlier cohort studies found no more cancers among stressed than unstressed members of the cohort. For example, Keehn et al found no greater cancer mortality among 9,813 soldiers of World War II discharged for psychoneurosis than among 9,942 controls over the period January, 1946, to December, 1969.
Keehn studied cancer mortality among prisoners of war in World War II from 1946 through 1975, and the Korean conflict from 1954 through 1978. No excess cancer mortality was found for either Pacific or European World War II veterans (n = 6,023), or for Korean veterans (n = 3,959) over their respective controls (n = 5,223 and n = 3,953).

Joffres et al looked at 4,581 Japanese men in Hawaii and found no more stressful events among cancer patients than among controls. While this is a case-control analysis, it should be noted that if such an analysis is done on all the cases and all the controls in a population, the results are no more biased than those in a cohort study, in which all the later cases and later controls are similarly identified. Stronger bias is found in smaller sample case-control studies in which both the controls and cases are selected. In the Joffres study, neither group was selected beforehand, and it could therefore be judged to be as trustworthy as a parallel cohort study.

Recent Cohort Studies–There have been relatively few recent cohort studies. An example is a study by Barraclough et al , who found no relationship between stressful events and breast cancer survival. In a widely cited series of studies, Grossarth-Maticek et al did find a relationship between stressful events and later cancer, but this work has been criticized most severely and will not be further dealt with here.

Readers should be aware of a demonstrated bias that may affect these studies . It appears that, on the whole, cancer patients tend to recall more stressful events than noncancer controls, even though some studies report otherwise . A few defining studies have shown that cancer patients’ reports of stressful events do not reflect actual events experienced. In a thorough review of memory as it is influenced by affect (that is, emotion, mood, or feeling), Blaney concluded that people with negative affect report more negative events than people with average or positive affect. Studies reflecting his conclusions are those of Brett et al and Cohen et al . Almost all patients who have cancer and know it have negative affect to varying degrees. Even if not all but a substantial number had negative affect, their excessive recall of negative events would be enough to bias the average recall level of the whole cancer group.

These three sets of findings lead us to the following conclusions :

1. Case-control studies yield mixed results but are subject to biases.

2. Most cohort studies show no excess stressful events associated with cancer incidence, mortality, or survival.

3. People with negative affect report having experienced more stressful events than those with average or positive affect, when the true frequencies are alike.

The last fact explains many, if not all, of the case-control findings. It is also the basis for predicting that in the absence of such bias, there will be no excess of stressful events among the cancer group. The prediction is confirmed by the findings of the cohort studies, in which that particular bias cannot exist. Thus, it is almost certain that stressful events do not occur more often among those who later get cancer, die of it, or survive a shorter time than among controls.

Bereavement

Bereavement is an important category of stress that has been studied for its possible effects on later cancer incidence and mortality. Holmes and Rahe ranked loss of spouse as the most stressful among 43 possible stressful events. Yet, several writers have observed that bereavement is not always accompanied by sadness, distress, or regret. For example, the death of a spouse with a fatal and painful disease can produce relief rather than sadness or distress. Although the number of such cases is quite probably relatively small, I know of no studies on this matter.

An overall measure of the effects of bereavement combines data from those who are distressed by the death and those who are relieved. The result is conservative, since the possible effect of distress in producing cancer will be diminished overall by the lack of reported stress among those experiencing relief. The result will be even more conservative if the bereaved who are relieved at a close person’s death do, in fact, have reduced susceptibility to later cancer.

Some of the earlier case-control studies reported increased cancer incidence among widowed persons. These have been intensively analyzed, as have prospective studies up to 1986, and their problems and difficulties have been carefully delineated .

In the cohort studies, as before, the bias that may exist in case-control studies has been removed. None of the large cohort studies carried out over an extended period have shown excess cancer deaths in bereaved spouses, compared with still-married spouses. In the exceptions, the excess lasted 6 months, a year, or, in one study, as long as 2 years. Since the development time to diagnosis of most cancers is on the order of years–3, 10, 15–those findings could not have referred to cancer initiation. One such large cohort study, a 1987 Finnish study of 95,647 persons widowed in 1972 , showed no excess deaths during the subsequent 4 years among 7,600 cancer cases. One can ignore the excess mortality seen among widows in the first week following death and in the first month among widowers as not being attributable to cancer.

Another study, conducted in Washington County, Maryland, of 4,032 white persons widowed between 1963 and 1974 and followed for approximately 12 years showed no excess of cancer deaths. A third large cohort study looking at this question reported a similar lack of excess cancer deaths over 10 years among persons widowed in 1971. Here, the sample was 1% of the whole population of England and Wales, observed from 1971 to 1981. The authors write, “No peak of postbereavement mortality from malignant disease is clearly established in either sex “. In a fourth such study of 1,782 breast cancer patients–all those diagnosed in Denmark from March 1, 1983, to February 29, 1984–and 1,738 controls, Ewertz found no difference in the death rates of married and widowed patients.

In summary, while some studies have reported a short-term excess of cancer following bereavement, large cohort studies have not, in general, found excess cancer incidence or death over the long term. This conclusion is consistent with the previous one that stress other than bereavement cannot be said to increase later cancer incidence or death.

A few studies have looked at cancer survival among widows, eg, Neale , and one or two have included widowers’ survival. Also, one or two studies have looked at disease-free interval. However, the results have been mixed, some finding reduced survival among the widowed and some not. In either case, those results cannot be applied to the current issue-bereavement as a psychological factor-since none of the studies on survival even mention the time of bereavement in respect to the cancer diagnosis. Only one thing can be certain in these studies: the marital status of the patient at the time of cancer diagnosis. Thus, the cancer could have been detected 1 day after bereavement or 20 years after bereavement. This fact allows no conclusions to be drawn from the marital status studies with regard to bereavement as a psychological factor.

Stress can cause a number of physical health problems, however the evidence that it can cause cancer is weak. Some studies have shown a link between psychological factors such as stress and anxiety and an increased risk of cancer. On the other hand many studies have failed to find evidence that people who tend to be anxious or stressed are any more likely to develop cancer than people who are more relaxed. A meta-analysis study published in 2013 of work stress and cancer risk, found that work stress, measured by job strain (high demands and low control at work) was not associated with colorectal, lung, breast or prostate cancer. There does not appear to be any such thing as a cancer-prone personality.

Several explanations may account for apparent links between stress and cancer. For example, people under stress may develop behaviours such as smoking, overeating, or drinking alcohol, which are known risk factors for cancer. Likewise, someone who has a relative with cancer may have a higher risk for cancer due to genetic risk factors, not because of the stress associated with a family member’s diagnosis.

The fast-paced world we live in is a perfect driver of stress. The racing heart, knots in the stomach and vague sense of agitation are an unavoidable part of the human condition. But chronic stress can, over time, harm the body, causing everything from inflammation to cardiometabolic disease.

In some cases, stress may play a role in cancer. But just how tightly are these two conditions linked?

Studies suggest several ways that stress may influence cancer development, said Shelley Tworoger, an associate professor of population science at the Moffitt Cancer Center in Tampa, Florida. Tworoger spoke about these links during a talk earlier this month at the annual American Association for Cancer Research meeting in Atlanta.

In those who already have certain types of cancer, stress can accelerate progression and worsen outcomes, increasing evidence suggests. But “there’s more question” about whether or not chronic stress can cause cancer in the first place, Tworoger told Live Science.

Indeed, according to the National Cancer Institute, the evidence that stress can cause cancer is weak. Even so, “there’s a lot of biologic reasons to think that an association could exist,” Tworoger said. Here’s what we know about chronic stress and the risk of cancer.

Stress and the body

Acute stress is completely normal and helps us react to dangerous situations. For instance, if a “lion is chasing you or you’re almost in a car accident,” the body’s stress response makes your heart race, sharpens your vision and can thus help you survive, she said.

During a stressful situation, the body turns on two key pathways: the sympathetic nervous system, which triggers the fight or flight response, and the hypothalamic pituitary adrenal (HPA) axis, which releases a key stress hormone called cortisol.

In the short term, these two axes “turn on, help you get through whatever the situation was and then, usually when the stress abates, they turn back off again,” Tworoger said.

But chronic stress and distress (extreme anxiety, sorrow or pain) continuously activate these pathways and release stress hormones, “in a way your body wasn’t really designed for,” Tworoger said.

Past research has shown that chronic activation of both of these pathways can lead to changes in the body — including altered metabolism, increased levels of certain hormones and the shortening of telomeres, the caps at the ends of DNA that prevent damage. All of these changes could potentially influence the development and progression of cancer, she said during the talk.

The long-term release of stress hormones can also induce DNA damage and affect DNA repair, said Melanie Flint, a senior lecturer in immunopharmacology at the University of Brighton in the United Kingdom, who also spoke during the talk.

What’s more, chronic stress weakens the immune system. Since the immune system acts as the cleaning crew that destroys and mops up damaged cells with genetic or metabolic errors, a weakened immune system could be the doorway in for cancer cells, Toworoger said.

There is “growing evidence that chronic stress can affect the cancer risk and progression through immune dysregulation,” said Dr. Elisa Bandera, a professor and chief of Cancer Epidemiology and Health Outcomes at the Rutgers Cancer Institute in New Jersey, who wasn’t a part of the talk. But “I don’t think you can say that there is an established link.”

In fact, most evidence ties stress to cancer survival, not to the risk of getting cancer in the first place, she said.

Stress and cancer risk

It’s tricky to design a study to show that stress fuels cancer in part because the experience of stress is so subjective and hard to measure. Stress can also manifest itself in the body in very different ways depending on how an individual perceives and copes with it, Toworoger said

“Some people have a negative response to job stress and some people love being stressed out in their jobs,” Tworoger said. In fact, “they thrive on it.” This perception, in turn, affects how the body responds.

As a result, many human studies rely on associations — rather than cause and effect— to show a link between stress levels and cancer incidence.

Previous studies have suggested, for example, that chronic stress is associated with an increased risk of a number of cancers, including breast cancer and some gastrointestinal cancers.

A Japanese study published in 2017 in the journal Scientific Reports looked at the correlation between stress levels and cancer in more than 100,000 people. They found no association between short-term stress and cancer incidence, but found that individuals, specifically men, who consistently had high-stress levels for a long time had an 11% greater risk of developing cancer than those with consistently low stress levels.

In new research that has not yet been peer-reviewed, Tworoger and her team looked at the association between social isolation and ovarian cancer risk. They found that people who were socially isolated had about a 1.5-fold increased risk of developing ovarian cancer compared to those who weren’t. They also found that people who had more post-traumatic stress disorder (PTSD) symptoms had an increased risk of developing ovarian cancer.

Another analysis, to be published in a forthcoming issue of the International Journal of Cancer, scoured the literature for studies analyzing the association between work stress and cancer risk. They found a significant association between work stress and the risk of colorectal, lung and esophageal cancer — but no association with the risk of prostate, breast or ovarian cancer.

Will we ever know?

Many other studies have also found no association. For example, Tworoger and her team did not find an association with job strain and ovarian cancer risk in a 2017 study published in the journal Psychosomatic Medicine. What’s more, a study published in 2018 in the European Journal of Cancer categorized the link between stress and cancer as a “myth.”

Some experts think that it’s not the stress itself that’s causing the cancer, but the unhealthy behaviors that come with being stressed.

Indeed, “the general consensus seems to be that chronic stress does not cause cancer per se, but it can indirectly increase cancer risk,” through stress-related behaviors such as smoking or heavy drinking, said Firdaus Dhabhar, a professor in the department of psychiatry and behavioral sciences at the University of Miami, who was not a part of the talk.

Other unhealthy, stress-induced behaviors, such as eating a bad diet and not exercising, also increase the risk of certain cancers, according to the National Cancer Institute. Tworoger, however, thinks that skeptics are writing off the cancer-causing effects of stress too fast. Stress hormones can cause “other biologic effects that are involved in the development of cancer,” Tworoger said. So “I think we do need more studies before we can say if is a myth.”

Either way, there’s “more and more evidence” that decreasing stress can improve survival and quality of life for patients who already have or had cancer, Tworoger said. “This has generated interest in mindfulness yoga interventions for cancer survivors with promising results,” Bandera added.

And reducing stress and leading a healthy lifestyle is important for many reasons Tworoger said. We “don’t know that stress causes cancer, but we do generally know that identifying strategies to help cope with stress can be very positive,” Tworoger said.

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Originally published on Live Science.

Stress Triggers Tumor Formation, Yale Researchers Find

Stress induces signals that cause cells to develop into tumors, Yale researchers have discovered. The research, published online Jan. 13 in the journal Nature, describes a novel way cancer takes hold in the body and suggests new ways to attack the deadly disease.

Until now, most researchers believed that more than one cancer-causing mutation needed to take place in a single cell in order for tumors to grow. The Yale team, led by Tian Xu, professor and vice chairman of genetics and a Howard Hughes Medical Institute Investigator, illustrated that cancer-causing mutations can cooperate to promote tumor development even when they are located in different cells within a tissue.

“The bad news is that it is much easier for a tissue to accumulate mutations in different cells than in the same cell,” said Xu, who also is a researcher with the Yale Cancer Center and the Fudan-Yale Center for Biomedical Research at Fudan University in China.

The Yale team worked with fruit flies to study the activity of two genes known to be involved in development of human cancers: a gene called RAS that has been implicated in 30 percent of cancers, and a tumor-suppressing gene called scribble, which contributes to tumor development when mutated. Neither a mutated RAS nor the defective scribble alone can cause cancer. Researchers in the Xu lab previously showed that a combination of the two within the same cell could trigger malignant tumors.

However, the Yale team found that these mutations did not have to co-exist in the same cell to cause tumors. A cell with only mutant RAS can develop into a malignant tumor if helped by a nearby cell with defective scribble. They also found stress conditions such as a wound could trigger cancer formation. For instance, RAS cells developed into tumors when a wound was induced in the tissue. The culprit underlying both phenomena turned out to be a signaling process called JNK, which is activated by environmental stress conditions.

“A lot of different conditions can trigger stress signaling: physical stress, emotional stress, infections, inflammation – all these things. Another bad news for cancer” Xu said.

While the paper shows it is easier than previously thought for cancer to take root in the body, it also identifies new targets to prevent and treat one of the deadliest diseases in the developed world. The Yale team found that the JNK stress signaling travels from one cell to the next, but that the propagation can be blocked.

“Better understanding of the underlying mechanism causing cancer always offers new tools to battle the disease,” Xu said.

Ming Wu and Jose Carlos Pastor-Pareja of Yale are other authors of the study, which was funded by the National Cancer Institute and HHMI.

Can stress cause cancer?

We regularly review and evaluate newly published research into the causes of cancer in order to shape our health information. And there are key things we look out for to evaluate any new study.

What type of study is it?

Was the study looking at cells in a dish, animals or people? Studies in animals and cells can help scientists understand the basics of cancer but they cannot replicate how things will work in humans.

So, we focus more on studies in people as they can show with much more certainty how something affects the risk of developing cancer in humans. The best studies also account for other factors that could affect someone’s cancer risk, such as whether they smoke or drink.

How many people were in the study, and how long were they followed for? Studies involving only a handful of people aren’t likely to be as reliable, because results are more likely to happen by chance. And studies that only follow people for a short timeframe can miss any potential long-term effects. Therefore, we mainly look at studies that follow hundreds or usually thousands of people for a long time because they give results we can be surer of.

Who carried out the study and where is it published?

It’s important to see if a study was published in a scientific journal and was carried out by scientists that work for a university or known institute. This is because before researchers can publish their findings in a journal, other experts who were not involved in the study will check it is accurate.

How does the study fit in with previous evidence?

Some studies show conflicting results, but we evaluate any new study within the context of all the available research and give more weight to the most rigorous scientific studies.

How to spot fake news about cancer?

Sometimes news outlets can over-inflate stories about cancer, whether it’s a new treatment, or news on what could lower or increase your risk of developing the disease. You can use the same questions we discussed above to judge a study and news story yourself. For more tips on how to spot fake news visit our blog here.

Stress fuels cancer spread by triggering master gene

A new study from the US published in the Journal of Clinical Investigation finds that activation of a master gene called ATF3 that is important for helping cells adapt to stress may be involved in helping breast, and possibly other cancers spread to other parts of the body (metastasis).

With the vast majority of all cancer suffering and death associated with metastasis, researchers are keen to learn more about what causes it. The American Cancer Society says metastasis is the single most significant challenge to management of cancer.

Stress could be unifying theme in cancer spread

Previous studies have shown that stress is a risk factor for cancer, and for example, that psychological stress is linked to breast cancer aggressiveness.

And researchers already know that ATF3 is activated when all types of cells experience stressful conditions that threaten their ability to maintain a constant internal environment (homeostasis).

Under normal circumstances, triggering ATF3 protects the body from harm by causing normal cells to commit suicide if there is a risk they have become permanently damaged by the stressful conditions (eg lack of oxygen or irradiation).

When cancer cells first arise, the immune system recognizes them as foreign agents and enlists immune cells to attack them. In the early stages of cancer development this works. But then things go wrong: one reason is cancer cells start to send signals to immune cells that cause them to misbehave in a way that helps the tumor grow.

In the new study, researchers at Ohio State University show that cancer cells are able to switch on ATF3 in immune cells that have been summoned to tumor sites. The result is ATF3 then causes the immune cells to malfunction and allow cancer cells to escape from the tumor and spread to other parts of the body.

Senior author Tsonwin Hai, a professor of molecular and cellular biochemistry at Ohio, says:

“If your body does not help cancer cells, they cannot spread as far. So really, the rest of the cells in the body help cancer cells to move, to set up shop at distant sites. And one of the unifying themes here is stress.”

Study suggests cancer cells target AFT3 in myeloid cells

In previous work, Prof Hai and her team found expression of ATF3 was linked to poorer outcomes in 300 breast cancer patients.

When they examined tumor samples from those patients they were stunned to find expression of ATF3 in certain immune cells was tied to poorer outcomes whereas ATF3 in cancer cells showed no such link.

In the new study, the researchers investigated those clinical results further by conducting two experiments in mice.

They first injected breast cancer cells in normal mice and in mice that could not express ATF3 in any cells.

The breast cancer in normal mice spread to the lungs much faster and more extensively than it did in the mice lacking ATF3.

In the second experiment, the team repeated what they did in the first experiment, except that instead of mice that could not express ATF3 in any cells, they used mice that had been genetically engineered to lack ATF3 only in a group of immune system cells called myeloid cells.

The results of the second experiment were similar to those of the first experiment, leading Prof Hai and her team to write:

“In conclusion, we identified ATF3 as a regulator in myeloid cells that enhances breast cancer metastasis and has predictive value for clinical outcomes.”

Stress gene could be target for drugs to fight metastasis

If further studies confirm these findings, the team believe the stress gene could one day be a target for drugs that fight cancer spread.

In the meantime, Prof Hai says, they help us better understand how tumor cells hijack the body’s own resources to promote cancer survival and spread.

There are lots of ways to switch on ATF3 in cells, as well as the signals sent by cancer cells, a high-fat diet, radiation, chemotherapy, UV damage and even chronic behavioral stress, are others.

The team now plans to investigate further how these and other stressors affect immune cells through switching on ATF3, changing them from attacking cancer cells to helping cancer cells.

Written by Catharine Paddock PhD

What is the relationship between stress and cancer?

Research has long supported a connection between inflammation and cancer. But what scientists are now learning is the implication inflammation may have on the relationship between psychological stress and cancer. So far, research has stopped short of concluding that chronic stress causes cancer, but enough is understood about the association to suggest that being in a constant state of stress is a risk factor for cancer and its progression, and that inflammation is likely to blame. “Chronic stress creates something of a perfect storm where precancerous cells can grow and flourish,” says Ankur Parikh, DO, Medical Director of Precision Medicine at Cancer Treatment Centers of America® (CTCA).

Fight or flight

The natural stress response, often called the “fight or flight” reaction, occurs when the body encounters a perceived threat, such as a rustling in the bushes or a sudden, loud noise. When scared or caught off-guard, the body releases adrenaline, cortisol and other hormones. Adrenaline causes the heart rate and blood pressure to rise. Cortisol, the primary stress hormone, triggers an increase in sugars, or glucose, in the blood. Typically, the stress response is self-limiting, meaning hormone levels and, consequently, heart rate, blood pressure and sugar levels, almost immediately return to normal. But when the body is stressed on an everyday basis, by factors like a demanding work schedule or a cancer diagnosis, the stress responses don’t always shut off.

The amount of stress anyone may experience largely depends on the person. Someone whose fight- or-flight system doesn’t shut off may have an overactive stress response, caused perhaps by slight differences in the genes that control stress. Or the deficiency may be caused by past traumatic events, such as abuse suffered as a child. Either way, a stress response system that doesn’t turn off generally causes inflammation, which may increase the risk for several health problems, such as anxiety, depression, heart disease and cancer.

“What we’re finding is that when you’re stressed, your body releases a surge of hormones, including adrenaline and cortisol, that triggers various inflammatory responses,” Dr. Parikh says. “When you’re in a constant state of psychological stress, those triggers don’t shut off, which could lead to chronic inflammation and, potentially, cancer growth or cancer metastasis.”

A perfect storm

People with chronic inflammatory bowel disorders like Crohn’s disease and ulcerative colitis tend to have chronic inflammation, for example, and are at a higher risk for colorectal cancer. Crohn’s disease and ulcerative colitis are autoimmune diseases, which develop when the immune system attacks healthy cells in the body by mistake. “It’s a case of a hospitable environment being created where cancer cells can develop and grow,” Dr. Parikh says.

It’s the same type of environment that develops when someone is in a state of constant stress, Dr. Parikh says. “This isn’t a case where we know that a specific gene mutation predisposes you to a chronic inflammatory state, but there is a lot of literature linking chronic stress and chronic inflammation, which could lead to an ideal environment for cancer to develop, or, if it’s already present, to grow and spread.”

In patients who already have cancer,

studieshave found that stress is linked to tumor growth. “We know that high-stressed cancer patients tend to have a harder time in treatment and recovery, and it makes sense that cancer might be harder to treat or more aggressive in these patients,” Dr. Parikh says.

While more studies are needed to further clarify the connection, experts say the current body of research is enough to suggest a connection between stress, inflammation and cancer—especially in people who already have the disease. That means everyone, including patients, should do what they can to change their lifestyle to reduce stress, which may help to improve their overall health and lower their risk of certain cancers, Dr. Parikh says.

Learn more about inflammation’s cancer connection.

Questions People Ask About Cancer

How common is cancer?

About one-third of all people in the US will develop cancer during their lifetimes.

If you want to know how many men and women have the 10 most common types of cancers, see Cancer Prevalence: How Many People Have Cancer?

To learn more about the chances of being diagnosed with cancer, see Lifetime Risk of Developing Cancer.

The risk of developing most types of cancer can be reduced by changes in a person’s lifestyle, for instance, by staying away from tobacco, avoiding too much alcohol, limiting time in the sun, and being physically active and eating healthy foods.

There are also screening tests that can be done for some types of cancers so they can be found as early as possible – while they are small and before they have spread. In general, the earlier a cancer is found and treated, the better the chances are for living for many years.

Who gets cancer?

Over one and a half million new cancer cases are diagnosed each year. Anyone can get cancer at any age, but the risk goes up with age. Nearly 9 out of 10 cancers are diagnosed in people ages 50 and older. Cancer can be found in people of all racial and ethnic groups, but the rate of cancer occurrence (called the incidence rate) varies from group to group.

How many people alive today have ever had cancer?

Today, almost 17 million people alive in the United States have had some type of cancer. Some of these people are cancer-free; others still have it.

Years ago, most people who had cancer did not live very long. That’s not the case anymore. Every year more and more people survive cancer. This is especially true of children with cancer and those whose cancers were found early, before they spread.

The survival rates are different for people with different types of cancers. Some types of cancer grow very slowly. Some respond to treatment very well. Others grow and spread faster and are harder to treat. If you know someone who has cancer, keep in mind that what happens to them could be very different from what happens to someone else with cancer.

What causes cancer?

Things people do

Some cancers are caused by things people do or expose themselves to. For example, tobacco use can cause cancer of the lungs, mouth, throat, bladder, kidneys, and many other organs. Of course, not everyone who uses tobacco will get cancer, but it greatly increases a person’s risk. It increases their chance of developing heart and blood vessel disease, too.

Spending a lot of time in the sun without protection can cause skin cancer. Melanoma is a very serious form of skin cancer linked to UV light from the sun and tanning beds.

Other things people are exposed to

Radiation can cause cancer. For instance, people exposed to nuclear fallout have a higher cancer risk than those who were not exposed. Sometimes, radiation treatment for one type of cancer can cause another cancer to grow many years later. This is why doctors and dentists use the lowest possible doses of radiation for x-rays and scans (much lower than the doses used for cancer treatment).

Certain chemicals have been linked to cancer, too. Being exposed to or working with them can increase a person’s risk of cancer. Call us to learn more about the carcinogens (substances that cause cancer) that may be around you, or see the What Causes Cancer? section of our website.

Genes that run in families

About 5% to 10% of all cancers are linked to genes that are inherited from parents.

Bottom line

No one knows the exact cause of most cases of cancer. We know that certain changes in our cells can cause cancer to start, but we don’t yet know exactly how it all happens. Scientists are studying this problem and learning more about the many steps it takes for cancers to form and grow. See the “What Causes Cancer?” section of our website to learn more about the things that have been linked to this disease.

If you are interested in taking steps to help reduce your cancer risk, see the section below called “Can cancer be prevented?”

Can injuries cause cancer?

It’s a common myth that injuries can cause cancer. But the fact is that falls, bruises, broken bones, or other such injuries have not been linked to cancer. Sometimes a person might visit a health care provider for what’s thought to be an injury and cancer is found at that time. But the injury did not cause the cancer; the cancer was already there. It also sometimes happens that a person will remember an injury that happened long ago in the place cancer was found.

Rarely, burn scars can be the site of cancer many years after the burn has healed. Most often, skin cancer is the type that starts in a burn scar.

Can stress cause cancer?

Researchers have done many studies to see if there’s a link between personality, attitude, stress, and cancer. No scientific evidence has shown that a person’s personality or outlook affects their cancer risk.

There are many factors to look at in the relationship between stress and cancer. It’s known that stress affects the immune system, but so do many other things. Despite many studies, a link between psychological stress and cancer has not been found.

What are the risk factors for cancer?

A risk factor is anything linked to your chance of getting a disease, such as cancer. Different cancers have different risk factors. For instance, exposing skin to strong sunlight is a risk factor for skin cancer, but it’s not linked to colon cancer. Some risk factors can actually cause cancer, while others may simply be more common in people who get cancer. For example, old age by itself doesn’t cause cancer, but it is a risk factor.

Still, risk factors don’t tell us everything. Having one risk factor, or even many, does not mean that someone will get cancer. Some people with one or more risk factors never develop the disease, while others who do develop cancer have no known risk factors. Even when a person who has a risk factor is diagnosed with cancer, there’s no way to prove that the risk factor actually caused the cancer.

There are different kinds of risk factors. Some, like a person’s age or race, can’t be changed. Others are linked to cancer-causing factors in the environment. Still others are related to personal actions, such as smoking. Some factors influence risk more than others, and a person’s risk for cancer can change over time, due to factors such as aging or lifestyle.

Some of the major cancer risk factors that can be controlled:

  • Tobacco use
  • Diet
  • Physical activity
  • Weight
  • Alcohol use
  • Sun exposure
  • Environmental exposures, such as radon, lead, and asbestos
  • Exposure to infections such as hepatitis, HPV, and HIV

Overall, about 1 out of 5 cancers diagnosed in the US are related to excess body weight, physical inactivity, excess use of alcohol, and/or poor nutrition, and could be prevented.

Is cancer contagious?

In the past, people often stayed away from someone who had cancer. They were afraid they might “catch” the disease. But cancer isn’t like the flu or a cold. You can’t catch cancer from someone who has it. You won’t get cancer by being around or touching someone with cancer. Don’t be afraid to visit someone with cancer. They need the support of their family and friends.

You can get more details on this in Is Cancer Contagious?

Can cancer be prevented?

There’s no sure way to prevent cancer, but there are things you can do to help reduce your chances of getting it.

Tobacco

Many cancers might be prevented if people didn’t use tobacco.

Smoking damages nearly every organ in the human body and accounts for about 1 out of 3 cancer deaths in the US. Cigarettes, cigars, pipes, and oral (smokeless) tobacco products cause cancer and should not be used. People who use tobacco should try to quit. Studies clearly show that ex-smokers have less cancer risk than people who continue to smoke. When you quit smoking, it also reduces exposure to secondhand smoke for those around you.

It’s best to never use tobacco at all and to stay away from secondhand smoke, which also causes cancer – even in non-smokers.

See Stay Away from Tobacco for more on this.

Alcohol

Drinking alcohol is linked to a higher risk of certain types of cancer.

Some people think that certain types of alcohol are safer than others. But ethanol is the type of alcohol found in all alcoholic drinks, whether they are beers, wines, or liquors (distilled spirits). Overall, it’s the amount of alcohol that’s drunk over time, not the type of drink, which seems to be the most important factor in raising cancer risk.

If you drink, limit your intake to no more than 2 drinks per day for men and 1 drink a day for women. This may help curb your cancer risk. You can find out more in Alcohol Use and Cancer.

Drinking and smoking

The combined use of alcohol and tobacco raises the risk of mouth, throat, voice box, and esophagus cancer far more than the effects of either one alone.

Ultraviolet (UV) rays and sunlight

You can lower your chances of getting skin cancer by

  • Staying out of the sun between the hours of 10 a.m. and 4 p.m.
  • Wearing a hat, shirt, and sunglasses when you are in the sun
  • Using broad-spectrum sunscreen with a sun protection factor (SPF) of at least 30
  • Not using tanning beds or sun lamps

See Ultraviolet (UV) Radiation to learn more about the link between UV exposure and skin cancer and to learn how to protect yourself and the people you care about from UV skin damage.

Diet

We know that our diet (what we eat or don’t eat) is linked to some types of cancer, but the exact reasons are not yet clear. The best information we have suggests a lower cancer risk for people who:

  • Eat a lot of fresh vegetables and fruits (at least 2½ cups a day)
  • Choose whole grains rather than refined grains and sugars
  • Limit red meats (beef, pork, and lamb)
  • Limit processed meats (bacon, deli meats, and hot dogs)
  • Choose foods in amounts that help them get to and stay at a healthy weight
  • Limit alcohol intake to 1 alcoholic drink a day or less for women and 2 or less for men

We have a lot of information on how diet and physical activity can affect cancer risk. Call us or visit our website to learn more.

Does sugar feed cancer?

Sugar intake has not been shown to directly increase the risk of getting cancer, having cancer spread, or having it get worse (progress). Still, sugars and sugar-sweetened drinks add a lot of calories to the diet and can cause weight gain, which is linked to cancer.

Vaccines that help reduce cancer risk

We now know that some cancers are caused by infections, mostly viruses. One virus that’s clearly linked to cancer is the human papillomavirus (HPV). It’s been linked to cervical cancer, anal cancer, many genital cancers, and even head and neck cancers. (See HPV and Cancer for more details.)

There are vaccines to help prevent HPV infections. But most adults have already been infected with HPV, and the vaccines haven’t been proven to help people who already have HPV. Young people who are not yet sexually active should have a lower future cancer risk if they get one of the vaccines before they’re exposed to the virus. The American Cancer Society recommends the vaccines for girls and boys aged 11 and 12, though they can be given as young as age 9. Vaccination is also recommended up to age 26 in women, as well as in certain men who may be at higher risk for HPV infection. To learn more, see HPV Vaccines.

Early detection

To find cancer early, while it’s small and before it has spread, adults should have regular tests called cancer screening tests. These tests help health care providers find common cancers before they cause symptoms. For example, regular screening can find cancers of the breast, colon, rectum, cervix, mouth, and skin early. If cancer is found early, it can be easier to treat. Survival also tends to be longer for those with early cancer. Talk to a health care provider about which screening tests might be right for you.

You can learn more about things you can do to help find cancer early in American Cancer Society Guidelines for the Early Detection of Cancer.

How is cancer diagnosed?

A person’s signs and symptoms are not enough to know whether they have cancer. (See Signs and Symptoms of Cancer for more on this.) If your health care provider suspects cancer you will need more tests, such as x-rays, blood tests, or a biopsy. In most cases a biopsy is the only way to be sure whether cancer is present.

To do a biopsy a piece of the lump (tumor) or abnormal area is taken out and sent to the lab. There, a doctor who specializes in diagnosing diseases (called a pathologist) looks at the cells under a microscope to see if cancer cells are present. If there are cancer cells, the doctor tries to figure out what type of cancer it is and how fast it’s likely to grow.

Imaging tests can measure the size of the cancer and can often show if it has spread to nearby tissues. Blood tests can tell providers about your overall health, show how well your organs are working, and give information about blood cancers.

How is cancer treated?

Surgery, chemotherapy, and radiation are the 3 main types of cancer treatment. A person with cancer may have any or all of these treatments. In choosing a treatment plan, the most important factors are generally the type of cancer and the stage (amount) of the cancer. Other factors to consider include the person’s overall health, the likely side effects of the treatment, and the probability of curing the cancer, controlling it to extend life, or easing symptoms.

Surgery

Surgery is often the first treatment used if the cancer can be taken out of the body. Sometimes only part of the cancer can be removed. And, sometimes there may be risks to doing surgery for a cancer diagnosis. Radiation or chemotherapy might be used to shrink the cancer before or after surgery.

For more about surgery to treat cancer, see Cancer Surgery and Risks of Cancer Surgery.

Chemotherapy

Doctors use chemotherapy or “chemo” drugs to kill cancer cells. Usually, the drugs are given intravenously (IV or into a vein) or taken as a pill by mouth. Chemo drugs travel throughout the body in the bloodstream. They can reach cancer cells that may have spread away from the tumor.

See Chemotherapy to learn more about chemo and its effects.

Radiation therapy

Radiation therapy is treatment with high energy rays (such as x-rays) to kill or shrink cancer cells. The radiation may come from outside the body, called external radiation, or from radioactive materials placed right into the tumor (internal or implant radiation). Getting external radiation is a lot like getting an x-ray.

See Radiation Therapy to learn more.

Other types of cancer treatment

Other kinds of treatment you might hear about include targeted therapy, stem cell or bone marrow transplant, and immunotherapy. Hormone therapy is another type of treatment that’s sometimes used to treat certain kinds of cancer.

Clinical trials

Clinical trials are studies in which people volunteer to test new drugs or other treatments. In cancer treatment, clinical trials may be used to learn whether a new treatment works better than the treatments used today. For instance, clinical trials are used to see if adding a new drug to the standard therapy makes it work better. In studies like this, some patients get the standard drug(s) (which are the best available at the time) and the new one being tested, while other patients get the standard drug(s).

Clinical trials are one way to get “cutting-edge” cancer treatment. Contact us and talk to your cancer care team to learn more about clinical trials and whether one might be right for you.

How do doctors decide how to treat cancer?

Doctors consider each patient as an individual with personal preferences, and then make recommendations based on things like their own personal experience, current research, the goal of treatment (cure or control), and current cancer treatment guidelines .

One source of guidelines is the National Comprehensive Cancer Network (NCCN), an alliance of leading cancer centers around the world. Panels of experts from these centers sort through the research evidence and combine that with their own knowledge and experience to come up with the best available treatment options for each cancer, and usually for each stage and characteristic of a person’s particular cancer.

These findings are published in NCCN Clinical Practice Guidelines in Oncology, which provide a standard for care in the field of oncology. The guidelines address cancer treatment, cancer detection, risk assessment and reduction, and supportive care. They are updated on a regular basis.

The NCCN guidelines help patients and cancer care providers make the best choices about cancer care. They aren’t perfect, and they don’t apply in every case. But they do offer a roadmap to making sometimes difficult and increasingly complicated decisions.

NCCN Patient Treatment Guidelines are available at www.nccn.com, a website devoted to patients, caregivers, and their families.

What are the side effects of cancer treatment?

Each type of cancer treatment has different side effects. It’s hard to predict what side effects a person will have; even when people get the same treatment they can have different side effects. Some can be severe and others fairly mild. It’s true that some people have a tough time with cancer treatment, but many others manage quite well. And most cancer treatment side effects can be treated.

Chemo side effects

Short-term (and often treatable) side effects of chemo can include things like nausea and vomiting, appetite loss, hair loss, and mouth sores. Because chemo can damage the blood-making cells in the bone marrow, patients may have low blood cell counts. This can lead to:

  • Higher risk of infection (from a shortage of white blood cells)
  • Bleeding or bruising after minor cuts or injuries (from a shortage of blood platelets)
  • Anemia (from low red blood cell counts), which can cause tiredness, shortness of breath, pale skin, and other symptoms

(See Understanding Your Lab Test Results for more details in blood counts and what they mean.)

Cancer care teams work carefully with patients to manage the side effects of chemo. Most chemo side effects go away after treatment ends. For example, hair lost during treatment usually grows back after treatment is over.

Radiation side effects

Radiation treatments are much like x-rays and are not painful. The most common side effects are skin irritation in the treatment area and fatigue. Fatigue is a feeling of extreme tiredness and low energy that doesn’t get better with rest. It often lasts for many weeks after treatment ends. Other side effects can happen, too, depending on what part of the body is being treated.

Is cancer treatment worse than cancer?

This is a belief that can be dangerous to many people when it affects whether they decide to get cancer treatment. People who think treatment is worse than cancer might not get the treatments that can save their lives.

A person who is thinking of refusing cancer treatment due to fear of side effects or other concerns should talk with a health care provider to clearly understand the likely outcomes of both treatment and non-treatment before making a decision.

If cancer is allowed to progress without treatment, symptoms get worse and new symptoms build up over time. Symptoms differ based on the type of cancer and where it is. Later in the course of cancer, when more serious symptoms start, curative treatment may not be an option. Cancer kills by invading key organs (like the intestines, lungs, brain, liver, and kidneys) and interfering with body functions that are necessary to live. Untreated cancer commonly causes death.

In contrast, cancer treatment often saves lives – especially when cancer is found and treated early. Even when it can’t cure the cancer, treatment can often help people live longer. And medical care can always be used to help a person feel better by reducing pain and other symptoms (palliative care). It’s important that a person knows the goal of each course of treatment, and makes informed decisions throughout the cancer experience.

There are times when every person being treated for cancer questions their commitment to the difficulties that come with treatment and its side effects. Sometimes they get discouraged by the uncertainty of treatment and wonder if it’s worth it. This is normal. It may help to know that doctors are always learning better ways to work with patients to control side effects. And remember, each year brings advances in cancer treatments, too.

What is remission?

Some people think that remission means the cancer has been cured, but this isn’t always the case. Remission is a period of time when the cancer is responding to treatment or is under control.

In a complete remission, all the signs and symptoms of cancer go away and cancer cells can’t be detected by any of the tests available for that cancer.

It’s also possible for a patient to have a partial remission. This is when the cancer shrinks but doesn’t completely disappear.

Remissions can last anywhere from several weeks to many years. Complete remissions may go on for years and over time the cancer may be considered cured. If the cancer returns (recurs), another remission may be possible with more treatment.

Can cancer be cured?

Many cancers can be cured, but not all of them and not always.

Cure means that treatment has made the cancer go away, and there’s no chance that it will come back. It’s rare that a doctor can be sure that cancer will never come back. In most cases it takes time, and the longer a person is cancer free, the better the chance that the cancer will not come back.

In 1998, Gustavo Ayala, a young pathologist, landed at Baylor College of Medicine in Houston, Texas, ready to start to see patients. But his state medical license was delayed, and during 4 months of unexpected freedom, he found himself hunched over lab dishes, absorbed by a strange kind of cellular courtship.

Ayala hadn’t planned to do research full time, but a little-explored feature of cancer enticed him: the tendency of some cancer cells to wrap around nerves and grow along them. He had seen that “perineural invasion” in cancer patients and knew it often signaled an aggressive tumor and a poor prognosis. “But nobody knew how it happened,” Ayala says. “There was no biology.”

So Ayala put spinal nerves from a mouse in a dish next to human prostate cancer cells. What he saw was a symbiotic dance: Before the cancer colony invaded the nerves, the nerves reached out to the cancer. They elongated toward the cancer cells and grew into the colony’s midst. In turn, the cancer cell colony ballooned. The attraction, it seemed, was mutual.

Since that observation, Ayala’s group and others have discovered that the peripheral nerves that branch through our bodies and regulate our organs are crucial partners to cancer as it grows and spreads. Those nerves churn out molecules that appear to aid the growth of cancer cells, and they alter surrounding tissue in ways that can make it more hospitable to cancer. “They’re not a bystander,” says Paola Vermeer, a cancer biologist at Sanford Research in Sioux Falls, South Dakota, who studies cancer-nerve interaction. “They’re an active participant in the disease process.”

To some experts, those revelations from basic biology help explain a controversial link between chronic stress and cancer progression. The work has also prompted several clinical trials testing whether blocking nerve signaling slows tumors’ spread. Those studies have yet to show long-term benefits for patients, but optimism is high. “The field, I feel, is about to explode,” Vermeer says. “People are starting to take notice.”

A dangerous partnership

Recent studies have revealed many lines of communication between tumors, nerves, and other nearby cells. Their elaborate crosstalk seems to promote the growth and spread of cancer, in part through the release of stress-related hormones.

Sympathetic nerves branching through the body release the hormone norepinephrine into nearby tissue. When it hits receptors on cancer cells, it can set off a signaling pathway that prompts growth. Green light for growth Norepinephrine released by nerves activates receptors on the endothelial cells that make up blood vessels. That signal prompts the formation of new blood vessels that can bring much-needed oxygen into a growing tumor. New blood Nerves can prompt certain immune cells to stand down. Some of their signals seem to nudgemacrophages into a mode that promotes cancer growth.They may also prevent T cells from attacking cancer cells directly. Extra protection Cancer cells release neurotrophicfactors—molecules that encourage nerves to branch and elongate toward the tumor. Luring nerves Norepinephrine Macrophage Neurotrophicfactor Tumor cells Nerve cell Blood vessel Tumor C. BICKEL/SCIENCE

It’s not outlandish to think the nervous system could become complicit in cancer’s growth and spread. Cancer is adept at exploiting the body’s normal functions—for example, by stimulating the growth of new blood vessels that nourish the invading cells. The disease manages to “curate the best of the body and use it to promote its survival advantage,” says Paige Green, head of the National Cancer Institute’s research program on basic biobehavioral and psychological sciences in Bethesda, Maryland. By studying how cancer “curates” protective mechanisms in the immune system, scientists have developed powerful drugs to thwart those mechanisms, sparking a multibillion-dollar industry.

The role of nerves has taken longer to emerge, says cancer neurobiologist Hubert Hondermarck of the University of Newcastle in Australia. Before the development of precise ways to label neurons, the small nerve branches in and around tumors were easy to overlook. And even after those tools were available, “There was no particular interest in studying nerves in depth among the cancer community,” Hondermarck says.

Many cancer labs were absorbed in studying genetic mutations in cancer cells themselves, not the body’s cancer-promoting signals, Ayala says. In the early 2000s, his focus on cancer-nerve crosstalk made him an outsider. “I was called the nerve guy.”

But Ayala wasn’t truly alone. Others were studying nerves in hopes of pinning down an elusive connection between cancer and stress. One such researcher was Anil Sood, a cancer biologist at the University of Texas MD Anderson Cancer Center in Houston. He was intrigued by findings that tumors grew bigger and faster in lab animals that were stressed—for example, by being physically restrained or socially isolated. Some studies had even suggested chronic stress in people made cancer more likely to progress. But how those proposed links worked wasn’t clear, he says. Among researchers interested in stress and cancer, “There was a feeling that hardcore scientists would view these kinds of observations to be ‘soft science.’”

So Sood and others went hunting for mechanisms. The researchers focused on the sympathetic nervous system, which orchestrates our “fight or flight” response to a perceived threat. The hormones epinephrine and norepinephrine play a key role in the response, increasing heart rate and blood pressure. Sympathetic nerves, which weave through our organs and signal to them, release those hormones into nearby tissue. (The adrenal glands perched on our kidneys secrete the same hormones into the bloodstream, which distributes them widely.)

Many cells in the body, including many cancer cells, are studded with β-adrenergic receptors, to which epinephrine and norepinephrine bind. And activating those receptors on cancer cells seems to encourage them to grow. In 2006, Sood’s team reported it could prompt a mouse’s ovarian tumor to grow larger by either exposing mice to chronic stress or giving the animal a drug that activates β-adrenergic receptors. Both interventions prompted cancer cells to recruit and nourish nearby blood vessels that, in turn, fueled their growth. Blocking the receptors prevented this growth.

That study and others showed cancer cells were alert to signals from the nervous system. Then, in 2013, research oncologist Claire Magnon and colleagues in the lab of cell biologist Paul Frenette at Albert Einstein College of Medicine in New York City went further. The researchers revealed that the small nerve fibers near a tumor were, at least sometimes, essential to the tumor’s growth. The team grafted human prostate tumors into mice and then either sliced out the surrounding nerves or destroyed them with a toxic chemical. Without neighboring nerves, the tumor failed to grow. In people, the team found that the higher the density of nerves in and around a prostate tumor, the faster the tumor tended to spread outside the prostate and the faster the cancer tended to recur after surgery. Studies by other groups showed that removing nerves could also prevent gastric and pancreatic tumors from forming. And at many other sites—including the breast, colon, and lung—researchers correlated nerve density with more aggressive disease.

Gustavo Ayala has probed basic interactions between nerves and tumor cells that could lead to new therapies.

DWIGHT ANDREWS/MCGOVERN MEDICAL SCHOOL AT UTHEALTH

They also began to document the ways that cancer and nerves cozy up. Nerves entwined in blood vessels can hitch a ride into a tumor as it recruits blood vessels to supply it with oxygen. Cancer cells also produce molecular signals that can prompt nearby nerves to form new projections snaking into and around the tumor. Some evidence suggests signals from cancer can even prompt the body to make brand-new neurons from stem cells.

A provocative paper published in Nature this year showed that, in mice, neural precursor cells in the brain appear to migrate to a prostate tumor to supply it with neurons. The study, by Magnon, who is now at the French biomedical research agency INSERM in Paris, and collaborators, pointed to an unexplored path of communication between cancer and the central nervous system.

Why would cancer cells form alliances with nerves in the first place, tuning in to their signals and drawing them close? One idea is that a nerve-rich neighborhood is simply a friendly place for cancer, says Steven Cole, a genomics researcher at the University of California, Los Angeles. Because nerves expand and migrate regularly, they crank out molecules that encourage growth and motility—which a nearby cancer cell will gladly drink up. Cole’s group also found that signals from sympathetic nerves nudge immune cells called macrophages to deconstruct nearby tissue, secrete growth-promoting molecules, and recruit blood vessels. “The cancer cells love it,” he says.

Another idea is that listening to signals from sympathetic nerves helps cancer cells synchronize their invasion to periods of high stress, says neuroimmunologist Shamgar Ben-Eliyahu of Tel Aviv University in Israel. As cancer grows, it risks provoking T cells trained to attack and kill the body’s wayward cells, he explains. But when the body is on high alert and sympathetic nerves are most active, the immune system is tamped down. “If the tumor is smart enough to expose its cells to the immune system only when the immune system is suppressed, then it’s an advantage.”

Some researchers view evidence about the role of nerves as a long-awaited mechanistic link between stress and cancer. “The idea that tumors can be so controlled by these nerves—all of a sudden it really brings some clarity into why various types of stress can be so bad for people,” says Elizabeth Repasky, a cancer researcher at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Cole notes that when he and others talk of a cancer-promoting stress response, they don’t mean the psychological experience commonly referred to as stress. That fretful, frazzled mental state doesn’t align perfectly with the release of stress hormones into our tissues and veins, he says. Still, he and others believe a state of chronic threat or insecurity—when a person doesn’t know how to meet basic needs such as food, shelter, and companionship—can manifest in a physical reaction that may drive cancer.

“I see these patients … who are taking care of their small children, maybe their parents, are living on aid or assistance, and now have some malignancy,” says Jennifer Knight, a psychiatrist specializing in cancer at the Medical College of Wisconsin in Milwaukee. “They’re in a chronic fight-or-flight mode because they’re under heightened threat, not getting basic needs met.” Knight is investigating whether stress-induced nerve activity could help explain why people of lower socioeconomic status do worse after a cancer diagnosis, even after factors such as access to care are controlled for.

“There are still a lot of unknowns” about the stress-cancer link, Sood says. Nerve activity may promote cancer regardless of whether a person is under particular stress, he says, and nerves may be a driver only at particular stages in a tumor’s evolution.

A fundamental problem, Hondermarck adds, is that objectively measuring the intensity of stress or defining what kind of stressful experience is relevant to disease is hard. “The potential relationship between stress and cancer has been in the air for a long time,” he says, “but has never been really demonstrated.”

Regardless of the role of stress in cancer, targeting the nervous system with drugs might help treat the disease. Knight, Repasky, Frenette, and Sood are all investigating a common class of drugs called β blockers. Used since the 1960s to reduce blood pressure and treat cardiovascular disease, and sometimes prescribed to manage short-term anxiety, they block β-adrenergic receptors to keep heart rate low.

Some retrospective studies have reported that people who happened to be diagnosed and treated for cancer while taking β blockers had better prognoses than patients not taking the drugs. But other studies found no benefit. So, several groups have launched prospective trials to test β blockers more systematically. Ben-Eliyahu has focused on the drugs’ potential to prevent metastasis after surgery, when residual disease often lingers around the surgical site or in distant parts of the body. He wondered whether administering a β blocker alongside another drug to reduce the cancer-promoting inflammatory reaction to surgery could make any leftover cancer less likely to spread.

In 2017, his team published results from a clinical trial, conducted with Cole and other collaborators, that enrolled 38 women with breast cancer who were slated for surgery. Five days before the procedure, half started to take the β blocker propranolol and the anti-inflammatory drug etodolac. The study had too few participants to draw conclusions about survival or disease recurrence. But breast tumors from women getting the drug cocktail expressed fewer genes associated with metastasis than tumors of women taking placebo. Ben-Eliyahu says his group now has similar, unpublished results from 34 people with colorectal cancer.

The field, I feel, is about to explode. People are starting to take notice.

Larger trials are in the works. Ben-Eliyahu and colleagues have launched a trial at Israeli medical centers that aims to recruit 210 people with pancreatic cancer, some of whom will start to take propranolol and etodolac a few days before surgery to remove their tumors. The researchers plan to track survival over 5 years.

But the team is having trouble raising money for the trial, Ben-Eliyahu says. Other groups are struggling, too. “Those trials are really challenging for reasons that are incredibly annoying when you actually think about them,” Cole says: Industry sponsors don’t see a way to profit from drugs that long ago lost patent protection. “It’s hard to even recruit patients because their docs are all putting them on studies of these fabulously remunerative brand-new therapies, as opposed to this β blocker that my grandfather took when he had a heart attack or something,” he says.

β blockers aren’t the only option for targeting the nervous system’s role in cancer. Future studies might also explore the potential of antibodies that bind to and disable proteins released by cancers that promote nerve growth, Hondermarck says. And Cygnal Therapeutics, based in Cambridge, Massachusetts, is pursuing cancer treatments that target the interaction between cancer and nerves, though it has yet to share details of its strategy.

Two decades after his first curiosity project, Ayala—now at McGovern Medical School at the University of Texas Health Science Center in Houston—is still studying the cancer-nerve relationship and has begun to pursue possible therapies. Last year, his team reported in The Prostate that in four men with prostate tumors, injecting the nerve toxin botulinum into one side of the tumor prompted more cancer cells to die there than on the untreated side. He’s preparing to test the approach in a larger group of men.

Ayala is energized by the new enthusiasm for the field. That he has had to spend some time in the academic wilderness is “absolutely normal,” he says. But in his view, studies focused on sympathetic nerves barely scratch the surface of cancer-nerve interactions. Some research has suggested a role for parasympathetic nerves, which counteract sympathetic signals to return the body to rest, and for sensory nerves, which relay various stimuli to the brain. Ayala is preparing to publish a study on the influence of two more nerve types, defined by the proteins they express. He expects that dozens of distinct nerve types form complex—and consequential—partnerships with cancer.

“This is a story to be written by many people over the next 30 years,” he says. “There’s much more out there.”

*Update, 13 September, 11:05 a.m.: This story was updated to mention Claire Magnon’s role in the 2013 study.

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