Stress and cancer: Mindfulness is pivotal component to improve outcomes

Stress hormones are released when the body responds to physical, mental or emotional pressures.

These stress hormones — such as epinephrine and norepinephrine — increase blood pressure, heart rate and blood glucose levels.

Prior research suggests chronic stress may cause problems with the digestive system, as well as contribute to infertility, urinary issues and weakened immune systems. In addition, those with chronic stress are more susceptible to viral infections, headaches, sleep disturbances, depression and anxiety.

Although no definitive conclusions have been reached about whether stress causes cancer, research has shown that psychological stress can influence a tumor’s ability to grow and spread.

HemOnc Today spoke with Lorenzo Cohen, PhD, professor and director of the Integrative Medicine Program at The University of Texas MD Anderson Cancer Center, about the stress–cancer connection, the focus of recent research in this area, and the ways members of care teams can help patients manage their stress and improve their emotional well-being.

Lorenzo Cohen, PhD

Lorenzo Cohen

Question: Can stress cause cancer? 

Answer: This is quite complex. The evidence does not support the hypothesis that stress is an etiological factor, which implies there is a direct cause and effect. With that being said, there is a challenge with stress research in humans and — at a fundamental level — how one even defines stress. One of the challenges is that when we talk about the word “stress,” we often mean “stressor” — or the event itself. In other words, the loss of a loved one, loss of a job or moving are all “stressors,” and how we respond and cope with them is “stress.”

 

Q: Although evidence does not directly suggest a cause-and-effect relationship, you previously suggested stress makes your body more hospitable to cancer. How so?

A: This is where things get a little more complicated. There is very good evidence that suggests chronic stress has a profound negative effect on most physiological processes in the body. Some of these are very important in controlling and regulating cancer growth. Chronic stress results in suppression of cell-mediated immunity — the part of the immune system that is very important for helping to control cancer growth. In fact, a lot of the emerging, cutting-edge oncology research is looking at treatments to try to harness our immune system and specifically ramp up cell-mediated immunity to help control cancer growth.

We also know from the elegant research of Anil K. Sood, MD, professor and vice chair for translational research at The University of Texas MD Anderson Cancer Center, and colleagues that chronic stress has an impact on other cellular processes that are very relevant for controlling cancer growth.

Even more profound research in this area was published years ago from researchers led by Elizabeth Helen Blackburn, AC, FRS, FAA, FRSN, a biological researcher at University of California, San Francisco. They found that chronic stress can shorten your telomeres, which are directly related to biological age, essentially suggesting that stress can literally speed the aging process. Advancing age is one of the key risk factors for developing cancer. Also, shortened telomeres result in chromosomal instability, so when cells replicate, there is a higher chance for it to result in mutation, and there is a lot of evidence that suggests shortened telomeres are a risk factor for cancer. These are examples of how the biological system is linked with chronic stress and also linked with cancer.

 

Q: Can chronic stress help cancer grow or spread? If so, how?

A: The preclinical research is becoming clearer in this area, and the answer is quite definitive. Yes, chronic stress can help cancer grow and spread in the preclinical setting. There is evidence from various animal models indicating that chronic stress speeds the growth of cancers in in vivo models, and what researchers have been able to do is map the biological pathways responsible for this. One example in an animal model that focused on ovarian cancer showed the sympathetic nervous system activity increased due to chronic stress, with an increase in norepinephrine, which was driving the cancer process. When the animals were given beta blockers that blocked the effect of norepinephrine, the effects of stress disappeared.

The underlying mechanisms for such effects are complex and involve chronic activation of the sympathetic nervous system and the HPA axis.  Sustained elevations from these can result in diverse effects, including stimulation of cancer invasion, angiogenesis, inflammation, reduced anoikis, and even reduced efficacy of chemotherapy drugs. There also is emerging evidence that chronic stress may even be linked with neurogenesis.

 

Q: What recent research related to the potential cancer–stress connection have you found particularly compelling or informative?

A: We conducted a study examining how a person responds to the diagnosis of cancer early in the process. The study included more than 200 patients diagnosed with stage IV kidney cancer. Although unlikely to be curable, there was considerable variety with regard to prognosis and expected survival. We assessed depression at the time of diagnosis, and we found a link between the levels of depression and survival. We also conducted gene-profiling studies to compare blood samples from the most depressed patients with samples from those who were least depressed. We found that the patients who were most depressed had upregulation of pro-inflammatory genes and associated transcriptional regulators that have previously been linked to cancer progression and metastasis via tumor-associated macrophages. These differences were also seen within the tumor microenvironment. So, even down to the gene regulatory level, we are seeing that an emotional response like depression can have an impact on the way cells express different genes — and, of course, we know that cancer is a disease of inappropriate gene regulation. This is really where the oncology field needs to start moving.   

 

Q: How extensive has the research been into the potential association between stress and cancer? Are there more studies evaluating this subject now than, say, 10 years ago?

A: There are more studies examining the role of chronic stress and mental health as a risk factor for cancer, and more importantly for prognosis once someone is diagnosed with cancer. There probably is still controversy, although the evidence is becoming quite overwhelming that depression and other mood disorders are negative prognostic indicators, which has been found in patients with lung, ovarian, prostate, kidney, liver and breast cancers to name a few. Those meeting clinical screening criteria for depression do not live as long. We know now that depression and other mood problems can literally get under your skin and into your cells and have an impact on biological functioning. The National Comprehensive Cancer Network has even recommended that distress be the sixth vital sign. There is hope that if we can take better care of patients’ mental health, it would not only help to improve their quality of life but also their length of life.

 

Q: What are the biggest challenges in this type of research?

A: There are a lot of challenges in this area, not the least of which is that mental health is stigmatized in our society. Everyone believes that they understand what stress is and what it is not, and they overly simplify the nuances that are important to understand from a scientific perspective. One of the challenges is that, for a number of different reasons, people do not want to believe that mental health plays a role in disease and medicine. One of the challenges for our society as a whole in this area is that this concept of figuring out how a patient is doing emotionally and making sure they have the proper resources is not part of medical school education. However, probably the more challenging area is creating a culture shift in prioritizing mental health. A patient’s emotional well-being should be prioritized the same as receipt of chemotherapy is prioritized. Another challenge is to make sure we do not blame the patients if they are not doing well clinically.  For example, saying or thinking “if the patient was just less sad or more optimistic then they would be doing better.” Having a positive outlook is just one piece of the equation that could be associated with better coping and mental health, but we need to be careful and not blame patients. 

 

Q: How important is it for patients to identify ways to minimize or manage their stress, and who should they speak to for suggestions?

A: I believe it is critically important for patients to manage their emotional well-being and stress levels. That isn’t to say patients will not experience stress, as this is expected. Rather, it is the chronic stress that is unrelenting that can be quite damaging. The evidence suggests that if you are not managing your stress properly, you are literally speeding the aging process in a general sense and, in terms of patients with cancer, this has been associated with worse quality of life and worse clinical outcomes. There are many different things that individuals can do to manage their stress, from simple relaxation techniques and meditation to more conventional areas of mental health treatments such as working with a psychologist. At MD Anderson, a lot of our research focuses on the emerging field of mind–body practices, such as yoga and meditation. We know from various clinical trials that these are effective strategies for managing chronic stress. These are all practices that ideally are engaged in on a daily basis. It is not like taking a round of antibiotics, where the patient finishes the 5 to 10 days of pills, the pathogen is out of the body and everything is fine. Chronic stress is something we live with, so trying to damper sympathetic arousal on a daily basis is really what we are aiming for.

 

Q: Is there a reluctance on the part of patients to raise this subject? If so, how important is it for members of the care team to ask patients how they are feeling or coping?

A: I think there is reluctance on both parts of the equation. For patients, they do not want to “bother” the team with their emotional issues; they are at the hospital, after all, for cancer treatment.  For the health care team, they have not received much training or education in this area and believe they are not equipped to deal with the response that a patient will have. There is also the belief that it will take more time during the clinical consultation if they raise these issues. However, there is evidence to suggest this is not the case. There have been studies that show it does not increase time spent with the patient significantly, but it does increase satisfaction and lead to better outcomes in terms of managing patient stress. I believe that sometime in 2016 all accredited cancer programs will be required to screen patients for distress. .

 

Q: What other specific advice do you have for stress management in patients with cancer?

A: It depends on what the patient is experiencing and what the individual challenges are. Some people will need more structure, like working one on one with a psychologist, and others would benefit from the plethora of mind–body practices that are available, such as yoga, tai chi, art therapy or music therapy. From our perspective, the best intervention for managing stress is the one that you will do on a daily basis. Gardening can be a very meditative practice for some, but for others it is not at all meditative and causes more stress. This is an important area research-wise — developing targeted psychosocial programs that are individualized. Just as we are doing with conventional targeted therapy, we need to start to refine the types of approaches we use with different patients to manage stress and improve emotional well-being.

 

Q: Do you have any final thoughts on the link between stress and cancer?

A: One major focus we have at MD Anderson is on comprehensive lifestyle change. Along with managing stress to improve your outcomes, it is also important to have a healthy diet, exercise regularly and sit less, maintain a healthy weight, and have healthy sleep habits. These are all interrelated and, interestingly, a concept such as stress and how you are managing your life emotionally is a critical factor in being able to engage in these other healthy behaviors that we know are related to clinical cancer outcomes. The person who is chronically stressed is most likely to forgo exercise and have bad sleep patterns, and they may eat a less-than-desirable diet because of all of these emotional biological changes within the body. Mindfulness is really a pivotal component for trying to live an overall healthy lifestyle to improve cancer outcomes because stress is linked to all areas of our lives. – by Jennifer Southall

 

For more information:

Lorenzo Cohen, PhD, can be reached at Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Department of Palliative, Rehabilitation & Integrative Medicine, 1515 Holcombe Blvd., Unit 460, Houston, TX 77030; email: lcohen@mdanderson.org.

Disclosure: Cohen reports no relevant financial disclosures.

Stress hormones are released when the body responds to physical, mental or emotional pressures.

These stress hormones — such as epinephrine and norepinephrine — increase blood pressure, heart rate and blood glucose levels.

Prior research suggests chronic stress may cause problems with the digestive system, as well as contribute to infertility, urinary issues and weakened immune systems. In addition, those with chronic stress are more susceptible to viral infections, headaches, sleep disturbances, depression and anxiety.

Although no definitive conclusions have been reached about whether stress causes cancer, research has shown that psychological stress can influence a tumor’s ability to grow and spread.

HemOnc Today spoke with Lorenzo Cohen, PhD, professor and director of the Integrative Medicine Program at The University of Texas MD Anderson Cancer Center, about the stress–cancer connection, the focus of recent research in this area, and the ways members of care teams can help patients manage their stress and improve their emotional well-being.

Lorenzo Cohen, PhD

Lorenzo Cohen

Question: Can stress cause cancer? 

Answer: This is quite complex. The evidence does not support the hypothesis that stress is an etiological factor, which implies there is a direct cause and effect. With that being said, there is a challenge with stress research in humans and — at a fundamental level — how one even defines stress. One of the challenges is that when we talk about the word “stress,” we often mean “stressor” — or the event itself. In other words, the loss of a loved one, loss of a job or moving are all “stressors,” and how we respond and cope with them is “stress.”

 

Q: Although evidence does not directly suggest a cause-and-effect relationship, you previously suggested stress makes your body more hospitable to cancer. How so?

A: This is where things get a little more complicated. There is very good evidence that suggests chronic stress has a profound negative effect on most physiological processes in the body. Some of these are very important in controlling and regulating cancer growth. Chronic stress results in suppression of cell-mediated immunity — the part of the immune system that is very important for helping to control cancer growth. In fact, a lot of the emerging, cutting-edge oncology research is looking at treatments to try to harness our immune system and specifically ramp up cell-mediated immunity to help control cancer growth.

We also know from the elegant research of Anil K. Sood, MD, professor and vice chair for translational research at The University of Texas MD Anderson Cancer Center, and colleagues that chronic stress has an impact on other cellular processes that are very relevant for controlling cancer growth.

Even more profound research in this area was published years ago from researchers led by Elizabeth Helen Blackburn, AC, FRS, FAA, FRSN, a biological researcher at University of California, San Francisco. They found that chronic stress can shorten your telomeres, which are directly related to biological age, essentially suggesting that stress can literally speed the aging process. Advancing age is one of the key risk factors for developing cancer. Also, shortened telomeres result in chromosomal instability, so when cells replicate, there is a higher chance for it to result in mutation, and there is a lot of evidence that suggests shortened telomeres are a risk factor for cancer. These are examples of how the biological system is linked with chronic stress and also linked with cancer.

 

PAGE BREAK

Q: Can chronic stress help cancer grow or spread? If so, how?

A: The preclinical research is becoming clearer in this area, and the answer is quite definitive. Yes, chronic stress can help cancer grow and spread in the preclinical setting. There is evidence from various animal models indicating that chronic stress speeds the growth of cancers in in vivo models, and what researchers have been able to do is map the biological pathways responsible for this. One example in an animal model that focused on ovarian cancer showed the sympathetic nervous system activity increased due to chronic stress, with an increase in norepinephrine, which was driving the cancer process. When the animals were given beta blockers that blocked the effect of norepinephrine, the effects of stress disappeared.

The underlying mechanisms for such effects are complex and involve chronic activation of the sympathetic nervous system and the HPA axis.  Sustained elevations from these can result in diverse effects, including stimulation of cancer invasion, angiogenesis, inflammation, reduced anoikis, and even reduced efficacy of chemotherapy drugs. There also is emerging evidence that chronic stress may even be linked with neurogenesis.

 

Q: What recent research related to the potential cancer–stress connection have you found particularly compelling or informative?

A: We conducted a study examining how a person responds to the diagnosis of cancer early in the process. The study included more than 200 patients diagnosed with stage IV kidney cancer. Although unlikely to be curable, there was considerable variety with regard to prognosis and expected survival. We assessed depression at the time of diagnosis, and we found a link between the levels of depression and survival. We also conducted gene-profiling studies to compare blood samples from the most depressed patients with samples from those who were least depressed. We found that the patients who were most depressed had upregulation of pro-inflammatory genes and associated transcriptional regulators that have previously been linked to cancer progression and metastasis via tumor-associated macrophages. These differences were also seen within the tumor microenvironment. So, even down to the gene regulatory level, we are seeing that an emotional response like depression can have an impact on the way cells express different genes — and, of course, we know that cancer is a disease of inappropriate gene regulation. This is really where the oncology field needs to start moving.   

 

Q: How extensive has the research been into the potential association between stress and cancer? Are there more studies evaluating this subject now than, say, 10 years ago?

A: There are more studies examining the role of chronic stress and mental health as a risk factor for cancer, and more importantly for prognosis once someone is diagnosed with cancer. There probably is still controversy, although the evidence is becoming quite overwhelming that depression and other mood disorders are negative prognostic indicators, which has been found in patients with lung, ovarian, prostate, kidney, liver and breast cancers to name a few. Those meeting clinical screening criteria for depression do not live as long. We know now that depression and other mood problems can literally get under your skin and into your cells and have an impact on biological functioning. The National Comprehensive Cancer Network has even recommended that distress be the sixth vital sign. There is hope that if we can take better care of patients’ mental health, it would not only help to improve their quality of life but also their length of life.

 

Q: What are the biggest challenges in this type of research?

A: There are a lot of challenges in this area, not the least of which is that mental health is stigmatized in our society. Everyone believes that they understand what stress is and what it is not, and they overly simplify the nuances that are important to understand from a scientific perspective. One of the challenges is that, for a number of different reasons, people do not want to believe that mental health plays a role in disease and medicine. One of the challenges for our society as a whole in this area is that this concept of figuring out how a patient is doing emotionally and making sure they have the proper resources is not part of medical school education. However, probably the more challenging area is creating a culture shift in prioritizing mental health. A patient’s emotional well-being should be prioritized the same as receipt of chemotherapy is prioritized. Another challenge is to make sure we do not blame the patients if they are not doing well clinically.  For example, saying or thinking “if the patient was just less sad or more optimistic then they would be doing better.” Having a positive outlook is just one piece of the equation that could be associated with better coping and mental health, but we need to be careful and not blame patients. 

 

PAGE BREAK

Q: How important is it for patients to identify ways to minimize or manage their stress, and who should they speak to for suggestions?

A: I believe it is critically important for patients to manage their emotional well-being and stress levels. That isn’t to say patients will not experience stress, as this is expected. Rather, it is the chronic stress that is unrelenting that can be quite damaging. The evidence suggests that if you are not managing your stress properly, you are literally speeding the aging process in a general sense and, in terms of patients with cancer, this has been associated with worse quality of life and worse clinical outcomes. There are many different things that individuals can do to manage their stress, from simple relaxation techniques and meditation to more conventional areas of mental health treatments such as working with a psychologist. At MD Anderson, a lot of our research focuses on the emerging field of mind–body practices, such as yoga and meditation. We know from various clinical trials that these are effective strategies for managing chronic stress. These are all practices that ideally are engaged in on a daily basis. It is not like taking a round of antibiotics, where the patient finishes the 5 to 10 days of pills, the pathogen is out of the body and everything is fine. Chronic stress is something we live with, so trying to damper sympathetic arousal on a daily basis is really what we are aiming for.

 

Q: Is there a reluctance on the part of patients to raise this subject? If so, how important is it for members of the care team to ask patients how they are feeling or coping?

A: I think there is reluctance on both parts of the equation. For patients, they do not want to “bother” the team with their emotional issues; they are at the hospital, after all, for cancer treatment.  For the health care team, they have not received much training or education in this area and believe they are not equipped to deal with the response that a patient will have. There is also the belief that it will take more time during the clinical consultation if they raise these issues. However, there is evidence to suggest this is not the case. There have been studies that show it does not increase time spent with the patient significantly, but it does increase satisfaction and lead to better outcomes in terms of managing patient stress. I believe that sometime in 2016 all accredited cancer programs will be required to screen patients for distress. .

 

Q: What other specific advice do you have for stress management in patients with cancer?

A: It depends on what the patient is experiencing and what the individual challenges are. Some people will need more structure, like working one on one with a psychologist, and others would benefit from the plethora of mind–body practices that are available, such as yoga, tai chi, art therapy or music therapy. From our perspective, the best intervention for managing stress is the one that you will do on a daily basis. Gardening can be a very meditative practice for some, but for others it is not at all meditative and causes more stress. This is an important area research-wise — developing targeted psychosocial programs that are individualized. Just as we are doing with conventional targeted therapy, we need to start to refine the types of approaches we use with different patients to manage stress and improve emotional well-being.

PAGE BREAK

 

Q: Do you have any final thoughts on the link between stress and cancer?

A: One major focus we have at MD Anderson is on comprehensive lifestyle change. Along with managing stress to improve your outcomes, it is also important to have a healthy diet, exercise regularly and sit less, maintain a healthy weight, and have healthy sleep habits. These are all interrelated and, interestingly, a concept such as stress and how you are managing your life emotionally is a critical factor in being able to engage in these other healthy behaviors that we know are related to clinical cancer outcomes. The person who is chronically stressed is most likely to forgo exercise and have bad sleep patterns, and they may eat a less-than-desirable diet because of all of these emotional biological changes within the body. Mindfulness is really a pivotal component for trying to live an overall healthy lifestyle to improve cancer outcomes because stress is linked to all areas of our lives. – by Jennifer Southall

 

For more information:

Lorenzo Cohen, PhD, can be reached at Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Department of Palliative, Rehabilitation & Integrative Medicine, 1515 Holcombe Blvd., Unit 460, Houston, TX 77030; email: lcohen@mdanderson.org.

Disclosure: Cohen reports no relevant financial disclosures.