Updated: Jan 7
The Front Line: Emotions, Chronic Stress and Cancer Progression
Beyond considering the scientific, traditional and clinical rationale for any cancer therapy, a comprehensive approach to health and healing must take into account all the aspects of the individual which contribute to the well-being of the whole. Emotional environment is an all too often overlooked, yet vitally important, component to comprehensive care. It isn’t extreme or unscientific to state that without addressing the emotional well-being of the patient, family, household and environment in which the patient lives we are overlooking an important factor contributing to optimal immune function and survival.
Stress Hormones and Cancer Progression
Numerous studies have now been published which report the detrimental effects of stress hormones on immune function in human cancer patients. Our high stress lifestyles contribute to cancer development and progression, and these tumorgenic effects of long term stress have been duplicated in laboratory settings.
Research shows chronic stress and stress-related hormones are involved in development of the malignant phenotype contributing to malignant characteristics including inflammation, resistance to normal cell death signals, evasion of the immune system, angiogenesis (new blood vessel formation), tissue invasion and metastasis (spread to distant sites). The findings of numerous epidemiological studies that report beta-blocker usage to be positively associated with long term survival in cancer patients should be a wake-up call for this modern epidemic known as chronic stress.
Relevant to veterinary medicine is the question of how human stress, psycho-social dynamics within the household, and our modern lifestyle affects companion animals. How is our stress becoming a chronic stress stimulus in our pets?
The Science Behind Chronic Stress and Cancer Progression
It is well accepted that continuous exposure to stress stimuli results in unmitigated production of stress hormones which has a deleterious effect on health and immune function.
Catecholamines such as epinephrine and norepinephrine affect cancer cell survival and tumor progression. These catecholamines released from sympathetic nerve fibers (norepinephrine) and circulating blood (epinephrine) in response to stress stimuli activate β-adrenergic receptors in the tumor microenvironment and the surface of tumor cells.
This activation impacts cancer cell biology as well as immune function. The responses induced by β-adrenergic signaling up-regulate expression of genes involved in tumor metastasis, inflammation, angiogenesis, tissue invasion, epithelial-mesenchymal transition. Conversely, these signals down-regulate genes involved in anti-tumor responses and affect the function of Tumor-associated macrophages. These mechanism bring to light the scientific basis for the long-observed association between cancer and stress.
β-adrenergic receptors (β1, β2, β3) are present at many sites of tumor growth and metastasis. β-adrenergic signaling mediates biological activity in epithelial cells, vascular monocytes and pericytes, and many lymphoid and myeloid immune cells which are relevant in tumor growth and metastasis. One of the downstream effector systems stimulated by norepinephrine- and epinephrine-related β-adrenergic stimulation involves activation of protein kinase A (PKA). PKA regulates a wide array of cell processes including proliferation, apoptosis, metabolism, differentiation, angiogenesis and gene transcription.
While it seems convenient and logical based on the above information to look to drugs like beta-blockers to address the adverses effects of chronic adrenergic stimulation, it has been shown that cognitive-behavioral stress management focused on anxiety reduction and coping skills can reverse anxiety-related pro-inflammatory states and stress-related up-regulation of metastasis-associated genes in women with breast cancer. Cognitive-behavioral therapies were also associated with decreased mortality and increased disease-free interval in a number of human cancer patient studies. It, therefore, makes sense to consider how environmental and behavioral management of stressors in companion animals may similarly impact disease control in veterinary cancer patients.
There are many causes for chronic stress in our veterinary patients which can be logically identified by observing the typical stressors in a companion animal’s life. These would, primarily, include home environment (both emotional and physical) and diet. Additionally, the cancer therapies imposed upon them by well intentioned owners and clinicians, whether these treatments be conventional, alternative or “natural”, can also be a source of chronic stress. It is important not to overlook the experience of the pet in receiving these therapies.
One focus of my Integrative Oncology Consultations is considering the level of stress involved in administering the proposed cancer therapies in the context of the patient's personality. We discuss what we can do to mitigate these stressors, from both the perspective of the pet and the client.
Even a change in diet, for a finicky pet, can cause extreme stress to that pet from both the owner (indirectly) and the pet (directly). So while we may have scientific data or a history of tradition justifying and rationalizing our treatment regimen, it is never ideal to adhere to any cancer protocol without regard to the emotional aspects of the treatment from the perspective of the patient. These stressors should be weighed against the expected benefit of the therapies and whether the treatment is considered curative or palliative (sometimes called "comfort care"). The clinician’s or pet guardian’s desire to “do something” should never trump the overall well-being of the patient.
Your Pet Picks Up On And Experiences Your Emotions
Our emotional stress impacts our pets. We know from human childhood cancer studies that parental distress is associated with long-term distress in pediatric oncology patients. Children whose parents have ongoing chronic stress related to their child's diagnosis exhibit more signs of emotional distress. This illustrates the importance of inter-family dynamics.
Pets are part of the family too and they experience our emotions. A recently published study reported that dogs with cancer are significantly more likely to have shown signs of stress at home prior to diagnosis.
Pets detect our emotions. It is well recognized that dogs notice human emotional cues and discriminate between positive and negative emotions.
Dogs are able to perceive our emotions through their acute sense of smell. We transfer emotions to our pets via chemosignals, or chemicals our body produces as a result of different emotions that have a smell which our dog can detect. Dogs can actually tell the difference between positive and negative emotions and respond differently to different human emotions. When they detect chemosignals associated with anger or fear they respond differently than they do to those associated with happiness, which has it's own smell. Studies have documented that dogs then manifest or experience the emotions corresponding to those their human is experiencing.
Dogs also obtain emotional information from both auditory and visual cues, and integrate them into a coherent perception of human emotion. This means they pick up on your emotional state through your facial expressions, your body language, your tone of voice and the words themselves.
Imagine this scenario: Person is worried about Pet and strongly desires to change their diet to something new. Person puts new food in bowl and offers to Pet. Pet smells new food. Person stands there anxiously staring at Pet to see if they will eat the food. (Person usually puts food in bowl and walks away. Pet notices this new change in behavior and picks up on negative emotions from Person.) Pet senses and then mirrors Person's emotions. Pet feels stressed. Pet doesn't eat. Person feels stressed. Person doesn't want to eat.
Now imagine this scenario: Person is excited about the food they are feeding Pet and feels good about what they are offering. Person thinks about how much they love Pet and feels happy they have this moment with them. Person prepares food with these happy thoughts and feelings. Person talks to Pet in a happy voice and explains to them why this food is so good for them and how it is such a big treat they are really going to love. Pet watches Person prepare this new delicacy while picking up "happy" chemosignals and body language. Person puts food in front of Pet. Pet smells new food. Person walks away and goes about their normal behavior. Pet feels comfortable. Pet eats. Person feels happy. Pet feels happy.
There are many reasons a dog or cat may not want to eat, some of which are medical concerns and some of which may be related to pet preferences. Often medical tests reveal no obvious cause for reluctance to eat and numerous anti-nausea medications and food changes are not effective at resolving picky eating behaviors. Based on the information above, once we have ruled out a medical cause for poor appetite, we have to also consider how our own emotional state and behavioral changes around feeding time may be affecting our pet. This is just one example of how stress can play a role in the well-being of everyone involved in the care of a pet diagnosed with cancer.
Managing Your Stress Helps Your Pet Feel Less Stress
All of this research just goes to support the experience that many veterinarians have had in clinical practice. I can't tell you how many times the emotional distress and anxiety of a pet parent during a consultation or veterinary visit visibly affects their pet. It is common to see more anxious behavior in patients whose people are highly anxious. The anxiety exhibited by the pet is often attributed by the pet parent to being at the hospital, not realizing that their emotional state is also playing a role in their pet's behavior. The perception of their pet's anxiety often escalates their own, leading to a difficult cycle that makes conversations and veterinary visits even more emotionally and technically challenging for everyone involved.
While there is, undoubtably, some real stress that many pets experience from the veterinary visit itself, I've had a number of positive results in decreasing anxiety levels when I've had pet parents open to the idea that managing the stress they feel during the visits and at home can help their pet experience less stress. They put effort into learning to develop skill in self-calming techniques and use those at home, on the way to the clinic and during the visit. For may pets, especially those who are not historically anxious, the positive results can be dramatic.
Although I am human and not always successful on a busy stressful day, I am always aware of how my emotional state affects my patients. I try to deliberately enter a room with as much calm as I can muster. I take a few deep breaths before entering, try to think of something positive, and try to be sensitive to the emotional environment of the room when I enter. When pets are exhibiting signs of fearfulness and anxiety at an initial consultation, for example, if time allows I usually try to sit and talk before approaching them. Many times if I can have a calm exchange with their person they often settle and show less signs of anxiety and fear. Sometimes they even come up to greet me or snuggle when that isn't normal behavior for them at a veterinary visit. My emotions can't often override the emotions of their person, especially if they are intense, as I believe pets are more acutely attuned to their people than a stranger. But the effort to maintain a calm emotional space can go a long way in improving the experience my patients have during a visit.
This is all just to illustrate that our emotions not only affect us and the humans in our life, they affect our pets too. This is about understanding. Notice if you are going toward thoughts or feelings of guilt, regret or blame. The point here is not to feel worse about having normal emotions associated with learning your pet has cancer. That isn't helpful or effective. The point is to develop an understanding of the dynamics that are at play in our well-being and the well-being of our pets. The point is to learn how we can positively impact each other and support each other while simultaneously supporting our own well-being. When we understand, we have information we can use to make choices and take positive action.
The good news is that happiness has it's own smell, or chemosignals. Happiness, just like negative emotions, can be transferred. So the efforts you make at developing a more stable emotional landscape and being able to hold happy, peaceful or calm emotional states more often can positively impact your pet during their healing process. If you can learn to "smell happy", your pet will be happier too.
Take a deep breath: Your breath is always available to you everywhere you go, and it's free. Deep breathing is proven to calm the nervous system and shift you from a state of stress ("fight or flight" sympathetic nervous system response) to a state of greater calm, allowing the parasympathetic nervous system (the "rest and digest" side of your nervous system) to engage.
Mindfulness for Stress Reduction Webinar Series: This is a series of three webinars I put together as a resource to help the people caring for my patients develop a toolbox to help them manage the normal stress they experience and find more well-being. These webinars are free on the Self-Care Webinars tab in the Metta Pets menu.
Professional Help: Taking care of your emotional self is extremely important. There is nothing wrong with seeking professional help when you are experiencing intense emotions that have become challenging for you to manage. Many people neglect to seek out help due to a fear of appearing weak, fragile or "broken". In fact, taking steps to seek the help you need to be healthy is a great sign of strength. It is also the most compassionate thing you can do for yourself, your pet, and everyone else in your life. We all need a little help once in a while. Fortunately there are people who have dedicated their life to helping us when we are in need of assistance learning how to find balance during challenging times.
Eng JW, Kokolus KM, Reed CB, et al. A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response. Cancer Immunol Immunother. 2014 Nov;63(11):1115-28.
Flint MS, Baum A, Episcopo B, et al. Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts. Stress. 2013 Jan;16(1):114-21.
Flint MS, Baum A, Chambers WH, et al. Induction of DNA damage, alteration of DNA repair and transcriptional activation by stress hormones. Psychoneuroendocrinology. 2007;Jun;32(5):470-9.
Lutgendorf SK, Andersen BL. Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions. Am Psychol. 2015 Feb-Mar;70(2):186-97.
Kim-Fuchs C, Le CP, Pimentel MA, et al. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain Behav Immun. 2014 Aug;40:40-7.
Lamkin DM, Sloan EK, Patel AJ, et al. Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling. Brain Behav Immun. 2012 May;26(4):635-41.
Cole SW, Sood AK. Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer Res. 2012 Mar 1;18(5):1201-6.
Tang J, Li Z, Lu L, et al. β-Adrenergic system, a backstage manipulator regulating tumour progression and drug target in cancer therapy. Semin Cancer Biol. 2013 Dec;23(6 Pt B):533-42.
Obeid EI, Conzen SD. The role of adrenergic signaling in breast cancer biology. Cancer Biomark. 2013;13(3):161-9.
Krizanova O, Babula P, Pacak K. Stress, catecholaminergic system and cancer. Stress. 2016 Jul;19(4):419-28.
Daly CJ, McGrath JC. Previously unsuspected widespread cellular and tissue distribution of β-adrenoceptors and its relevance to drug action. Trends Pharmacol Sci. 2011 Apr;32(4):219-26.
Baker JG, Hill SJ, Summers RJ. Evolution of β-blockers: from anti-anginal drugs to ligand-directed signalling. Trends Pharmacol Sci. 2011 Apr;32(4):227-34.
Lee BY, Timpson P, Horvath LG, et al. FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther. 2015 Feb;146:132-49.
Armaiz-Pena GN, Allen JK, Cruz A, et al. Src activation by β-adrenoreceptors is a key switch for tumor metastasis. Nat Commun. 2013;4:1403.
Antoni MH, Lutgendorf SK, Blomberg B, et al. Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics. Biol Psychiatry. 2012 Feb 15;71(4):366-72.
Stagl JM, Lechner SC, Carver CS, et al. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up. Breast Cancer Res Treat. 2015 Nov;154(2):319-28.
Antoni MH. Psychosocial intervention effects on adaptation, disease course and biobehavioral processes in cancer. Brain Behav Immun. 2013 Mar;30 Suppl:S88-98.
Maurice-Stam H, Oort FJ, Last BF, et al. Longitudinal assessment of health-related quality of life in preschool children with non-CNS cancer after the end of successful treatment. Pediatr Blood Cancer. 2008 May;50(5):1047-51.
Barrera M, Atenafu E, Andrews GS, et al. Factors related to changes in cognitive, educational and visual motor integration in children who undergo hematopoietic stem cell transplant. J Pediatr Psychol. 2008 Jun;33(5):536-46.
Yağci-Küpeli B, Akyüz C, Küpeli S, et al. Health-related quality of life in pediatric cancer survivors: a multifactorial assessment including parental factors. J Pediatr Hematol Oncol. 2012 Apr;34(3):194-9.
Albuquerque N, Guo K, Wilkinson A, et al. Dogs recognize dog and human emotions. Biol Lett. 2016 Jan;12(1):20150883.
Semin GR, Scandurra A, Baragli P, Lanatà A, D'Aniello B. Inter- and Intra-Species Communication of Emotion: Chemosignals as the Neglected Medium. Animals (Basel). 2019 Oct 31;9(11).
Müller CA, Schmitt K, Barber AL, Huber L. Dogs can discriminate emotional expressions of human faces. Curr Biol. 2015 Mar 2;25(5):601-5.
Siniscalchi M, d'Ingeo S, Quaranta A. The dog nose "KNOWS" fear: Asymmetric nostril use during sniffing at canine and human emotional stimuli. Behav Brain Res. 2016 May 1;304:34-41.
D'Aniello B, Semin GR, Alterisio A, et al. Interspecies transmission of emotional information via chemosignals: from humans to dogs (Canis lupus familiaris). Anim Cogn. 2018 Jan;21(1):67-78.
de Groot JH, Smeets MA, Rowson MJ, et al. A sniff of happiness. Psychol Sci. 2015 Jun;26(6):684-700.