Stress Responses 1
Running head: STRESS RESPONSES
Stress Responses and Worries of Women at Risk for Breast Cancer
Czarina E. Sánchez
Vanderbilt University
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ABSTRACT
The physiological impact of a breast cancer discussion between mothers and their daughters was
analyzed in relation to other anxiety and concern measures. Fifty-eight mothers with varied
breast cancer histories participated. Measures of general anxiety (BAI), concern about breast
cancer (IES), perceived risk, and observational data were correlated to salivary cortisol and
norepinephrine measured by alpha-amylase. Analysis revealed that cancer specific worries but
not general anxiety were positively correlated to cortisol levels, specifically IES-intrusion
subscale scores, but not IES-avoidance. Observed behavioral anxiety and avoidance during the
interaction did not show significant correlations. However, exploratory analyses revealed
whine/complain behavior to be positively correlated with cortisol levels.
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Stress Responses and Worries of Women at Risk for Breast Cancer
INTRODUCTION
The relationship between stress and cancer development has not been firmly established.
Large scale meta-analyses have found only a weak connection between the two. However, stress,
especially in the minds of many women with breast cancer, seems to have a direct connection
with the development of cancer. For example, stress was the most attributed cause of breast
cancer in a survey of 400 women with the disease (Steward, Cheung, Duff, Wong, McQuestion,
Cheung, et al., 2001). Because of the mixed findings in the literature with respect to the effect of
psychological factors in the progression of breast cancer, it is imperative to seek out information
to clarify the relationship. By better understanding stress reactivity in women in relation to a
breast cancer related task, this study will shed light on this debated topic and offer some
clarification to issues of the mind and body connection. The prevalence and effects of breast
cancer make it important to better understand the role of emotions and psychological stress
reactions in women at risk.
Breast Cancer
The chance for a woman in the United States of developing breast cancer during her
lifetime is one in eight. Breast cancer is the most common cancer among women besides skin
cancer (American Cancer Society, 2007). It is also the second leading cause of cancer death in
women. In 2007, an estimated 178,480 women in the United States will be diagnosed with
invasive breast cancer. Further, about 40,460 women will die from breast cancer in this year
alone. The incidence of breast cancer has continually increased since 1980 although the rate of
increase of new cases has leveled off in recent years.
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Cancer is the abnormal growth of cells due to damaged DNA that develops from
inherited abnormalities or environmental triggers. Most breast cancers begin with the
development of a malignant tumor at the cells of the glands or ducts in the breast (American
Cancer Society, 2007). The diagnosis of breast cancer is carried out by analysis of imaging tests
and biopsies. The analysis is necessary for the complex process known as staging which means
determining the size of the tumor and extent of spread of the cancer. Staging is essential because
treatment options are based on the stage of the cancer. The more widespread the cancer is, the
lower the relative survival rate, which can be as low as 20% for the more advanced cases.
The treatment options are divided into two categories: local and systemic. Local
treatment is designed to treat the cancer without affecting the rest of the body through surgery or
radiation (American Cancer Society, 2007). The purpose of surgery is to directly remove the
cancer cells. Surgery types range from lumpectomy which is the removal of only the tumor, to
radical mastectomy, the removal of the whole breast, underarm lymph nodes, and chest muscles.
These options can lead to increasing disfigurement and side effects. Radiation uses high-energy
rays from external sources or from radioactive materials placed directly on the tumor to kill
cancer cells. Systemic treatments are given by mouth or injected into the bloodstream to reach
cancer that is more spread out in the body (American Cancer Society, 2007). Some examples of
systemic treatments are chemotherapy and hormone therapy. In chemotherapy, anticancer drugs
are introduced into the system to kill the cancer cells. However, because chemotherapeutic
agents are designed to identify and kill all rapidly growing cells, many normal cells are also
killed in the process causing side effects of fatigue, hair loss, nausea, vomiting, and sometimes
permanent changes in menstrual cycle. After chemotherapy many women also experience painful
sensations and some loss of physical functioning. Hormone therapy is used in cases where
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estrogen is the promoter of cancel cell growth and blocking this hormone can be a treatment
option. However, the treatment can cause the spread of cancer into the lining of the uterus and
alterations to the woman’s cycle.
It is clear from this brief summary that the diagnosis of breast cancer and the consequent
treatments are accompanied by serious physical trials. However, it is not only the physical effects
of breast cancer that have a dramatic influence on the women’s wellbeing. Cancer can also be
accompanied by significant emotional toil. Depression and anxiety are often experienced by
women faced with cancer (e.g., Epping-Jordan, Compas, & Howell, 1994). These feelings can be
the result of changes in body image, the inability to work or care for the family, and fears that
develop from the cancer diagnosis. Cancer is also closely associated with the threat of death. All
these feelings can have a large psychological impact on a woman’s life.
Risk Factors for Breast Cancer
There are different risk factors for breast cancer and even though they do not mean a
certainty of cancer diagnosis, they indicate an increased chance of developing the disease.
Several of the risk factors cannot be changed. For example, the main risk factor is gender.
Simply being a woman drastically increases the chances of breast cancer. Age is also a factor
with the risk of breast cancer increasing significantly with age. About 77% of cancer diagnoses
are for women over the age of 50 (American Cancer Society, 2007).
The risk of breast cancer is also higher for women with a history of breast cancer in their
family. A woman’s risk doubles if a first degree relative such as a mother, sister, or daughter has
had breast cancer and is even greater if the cancer occurred before menopause. BRCA1 and
BRCA2 are two genes have been identified to take part in the development of cancer (American
Cancer Society, 2007). They are normally tumor suppressor genes but they can trigger cancer
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growth when mutated. These mutations can be inherited and 5-10% of cancer cases are due to
hereditary gene mutations of these genes. Women with inherited mutations have a risk of
developing breast cancer as high as 80%. The gene mutations can also develop from
environmental triggers. The processes however are yet to be identified.
Cancer, Cancer Risk, and Stress
The risk of developing cancer is two to three times greater for women with a positive
history of breast cancer than for women without first degree relatives who had breast cancer (Gil,
Mendez, Sirgo, Llort,Blanco, & Cortes-Funes, 2003). The increased risk due to a familial history
of breast cancer can become a chronic psychological stressor. Women with a history of cancer in
their families live under the constant threat of developing the disease themselves and suffering
the consequences aforementioned. For example, a study by Trask, Paterson, Wang, Satoru,
Milliron, and Blumberg (2001) found that two-thirds of women at high risk for breast cancer, out
of a sample of 197, had cancer related worries that interfered with their lives. These women also
reported higher levels of anxiety and a general decrease in mental health.
Another important factor is the presence of intrusive thoughts, defined as unwanted
images and strong waves of feelings in response to a specific stressor. Intrusive thoughts are
characteristic of a post-traumatic stress response to a cancer diagnosis or the treatment of the
disease. These uncontrollable worries are closely tied to unsuccessful efforts to avoid or
suppress unwanted thoughts or images about the disease. Studies have also shown that avoidant
thoughts about one’s cancer are related to poorer disease outcomes (Epping-Jordan, Compas, &
Howell, 1994). These authors found that cancer patients who were high in avoidance were 2.5
times more likely to suffer a recurrence of cancer or to die from the disease one year later, even
after statistically controlling for all relevant medical variables. Intrusive thoughts and avoidance
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may also be important processes to study in women at risk for cancer as well as in patients who
have been diagnosed with the disease.
Biology of Stress
In order to understand the potential role of stress in cancer, it is important to have a basic
understanding of the biological processes involved in the human stress response. The body’s
reaction to an acute stressor is set in order to prepare the body for an adequate response
(Sapolsky, 2004). One important aspect of this response is the rapid mobilization of energy
throughout the body. In response to stress, glucose production is increased while its storage in fat
cells is decreased. This is done in order to make glucose a readily available energy source for the
muscles needing it to react. Heart rate, breathing rate, and blood pressure also increase to
transport and provide the glucose and oxygen necessary throughout the body.
To best allocate these energy resources, the coordination of different systems takes place.
Areas of less critical importance are inhibited so that most resources go to the muscles, heart, and
brain which will coordinate the reaction to the stressor. The organs involved in digestion and
reproduction receive decreased circulation and fewer materials than under normal circumstances.
In this way the body focuses the energy supply on responding to the threat while long term
processes are momentarily halted for the more general safety of the body. The immune system is
also inhibited under stress, limiting the protection against other body aggressors. Cognitive
changes are also part of the stress response. They include decreased sensitivity to pain and
increased perception of the surroundings. All these reactions are known as the flight or fight
response because they prepare the body to react to the stressor in either of those ways. The
physiological activation of the stress response is mediated by two pathways in the body
(Sapolsky, 2004).
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Sympathetic Adrenal Medullary Axis. One of these pathways begins with the activation
of the sympathetic branch of the autonomic nervous system. The stressor is translated as an
emergency situation. The nerves of the sympathetic nervous system branch from the spinal
column out to the body. The nerve endings release epinephrine and norepinephrine which are
neurotransmitters that signal the organs to take the appropriate action necessary for the best use
of the energy resources. Epinephrine and norepinephrine are catecholamines made in the medulla
of the adrenal gland. The parasympathetic system is the other half of the autonomic nervous
system and acts in opposition to the sympathetic to suppress the stress response reactions when
adequate. It slows heart rate, breathing rate and directs flow to the digestive organs.
Hypothalamic-Pituitary-Adrenal Axis. The other way the body mediates the stress
response is through hormones of the Hypothalamic-Pituitary-Adrenal axis (HPA axis). The
hormones are secreted from different glands in the body and travel in the circulation to the
organs where they elicit certain reactions. The hypothalamus releases hormones that signal the
anterior pituitary gland to also release hormones. These in turn signal to other parts of the body
such as the cortex of the adrenal gland to release other hormones that will elicit the desired
response.
When an individual senses a stressor, the hypothalamus at the base of the brain is
activated and releases CRH (corticotropin releasing hormone) along with other hormones with
similar purpose. The hormones travel in the circulatory system between the hypothalamus and
pituitary and activate the anterior pituitary gland. It in turn releases ACTH (adrenocorticotropin
hormone) into the blood stream. Within a few minutes ACTH reaches and activates the adrenal
gland which rests on top of the kidneys. The adrenal cortex is stimulated to release cortisol.
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Cortisol has similar effects to epinephrine and belongs to the category of hormones known as
glucocorticoids, steroid hormones made in the adrenal cortex (Padgett &Glaser, 2003).
The two systems work in combination to bring about the fight or flight response.
However, the stress response is not a clear cut picture of fight or flight, as there are varied
responses to stress and gender differences in the physiology and psychology of stress (Sapolsky,
2004). There are further complications even when the same pathways are activated. Any stressor
can activate the same pathway, but they can be activated to different degrees and the hormones
released in different proportions. Variability in the response can also be brought about by
altering the hormone sensitivity of the different tissues.
Furthermore, in times when the stressor can neither be fought nor escaped, damage to the
body can be caused by the over and prolonged activation of the fight or flight response. Chronic
stress can therefore cause problems by the chronic activation of the cardiovascular system. The
decrease in resources available for the repair and growth mechanisms of the body leads to an
increased likelihood of disease. The energy that is taken up by the stress response means
decreased energy resources for use in other purposes. The body can be easily thrown off balance
due to the instability caused by the response activation.
Effect of Stress on Immune System
The susceptibility to disease is also increased due to suppression of the immune response.
As described in a review by Padget and Glaser (2003) the chronic activation of the stress
response results in chronic production of glucocorticoids and catecholamines. In excess, these
hormones interfere with normal immune cell activity. Immune cells have receptors for the
neuroendocrine products, the catecholamines, and the glucocorticoids of the stress response axes:
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the HPA and the SAM axes. Production of these regulates the immune response when necessary,
but overproduction can lead to health problems.
Stress Biology and Breast Cancer
Women at increased risk for breast cancer may be most affected by the emotional and
biological consequences of chronic stress. These processes have been addressed in a series of
studies by Bovberg and colleagues. Gold, Zakowski, Valdimarsdottir, and Bovberg (2003)
compared endocrine responses to a brief psychological stressor in women at familial risk for
breast cancer and women at normal risk. Thirty-six women at normal risk and 17 women at
familial risk were presented with a laboratory stressor not related to cancer, a speech task and
mental arithmetic task that took about 15 minutes. The control group consisted of 30 normal risk
women that did not participate in the tasks. Epinephrine, norepinephrine, and cortisol
measurements were taken from their blood plasma at baseline level, immediately after the stress
test, and 30 and 45 minutes after. The effect of the stress task was confirmed by their heart rate
responses. The results found were that women at familial risk for breast cancer had a stronger
and prolonged response post-stress task to epinephrine and cortisol as compared to normal risk
women. This was measured as the change from the control group’s baseline level. A significant
difference was not found in norepinephrine levels.
In a second study, James, van Berge-Landry, Valdimarsdottir, Montgomery, and Bovberg
(2004) provided further evidence that women at familial risk of breast cancer have an altered
response to stress due to the chronic life stressor of breast cancer threat. Urinary epinephrine and
norepinephrine excretion rates were measured in women at work, home and during sleep. The
comparison was between 73 women with familial risk and 81 women with normal risk of breast
cancer. The purpose of the study was to test the results obtained by Gold et al. in a naturalistic
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setting. It was found that women at familial risk of breast cancer showed increased epinephrine
at work likely due to an increased response to the daily stressors. An increase in the level from
sleep to work in both epinephrine and norepinephrine was also found. This shows that women at
familial risk had a stronger response to the acute stressors because of the chronic stressor of
being at increased risk for breast cancer.
Another study that gives further evidence to the increased stress reactivity of women with
familial history of breast cancer was carried out by Valdimarsdottir, Zakowski, Gerin, Mamakos,
Pickering, and Bovberg (2002). Sixteen women with family history of breast cancer and 32
women at normal risk participated in a 15 minute classic laboratory stressor. The task consisted
of a 5 minute taped speech that was performed in front of an experimenter and a 5 minute
arithmetic task where the participants were told they needed to work faster or harder. Seventeen
women at normal risk served as controls and were assigned a non-stressful task of reading two
articles and assured they would not be tested in any way. Self-reported distress was assessed
before and after. Heart rate and blood pressure were measured before, during, and after the tasks.
Natural killer cell activity (NKCA) measures were obtained from blood drawn before and
following the tasks. NKCA is an immune measure that seems to be correlated to emotional
distress.
Valdimarsdottir et al. (2002) found that women participating in the stressful task
experienced higher levels of distress and of those, the women with familial history experienced
even higher distress levels than women at normal risk. A similar effect was found in heart rate
reactivity with the women at familial risk having the highest increases. Blood pressure rose for
both types of women in the stressor task showing the task did have an effect. There was no
significant difference found between the two groups though. The women with familial history of
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cancer did show larger increases in NKCA concentration as compared to women at normal risk
who in turn had a higher concentration than women in the non-stressor task. The results indicate
that the women at familial risk of breast cancer have a heightened psychobiological reactivity to
the laboratory stressor. This is further support for the risk of breast cancer working as a chronic
life stressor and causing changes in the body’s response to other stressors.
The studies by Bovberg and colleagues are important in establishing that women at
increased risk for breast cancer show a heightened physiological response to stress. This
suggests that the chronic psychological stress associated with being at risk for breast cancer may
contribute to greater sensitivity and reactivity to stress. These studies are limited, however, in
their focus on immune system responses to the effects of stress hormones. There is presently no
clear evidence that the immune system plays a central role in the regulation of the development
of cancer cells. Further, these studies examined the effects of general types of stress and did not
examine sources of stress that may be specifically related to the threat or risk of developing
breast cancer. Breast cancer related stressors may present a particularly important set of
demands to women who are at risk for the disease.
Purpose of the Present Study
The lack of understanding of the relationship between stress and cancer and its
importance to the lives of so many women makes increasing the knowledge on the subject a
pressing need. Previous research has been limited in several ways. For example, previous
researchers have used laboratory stressors that are unrelated to breast cancer. The study will
provide a deeper understanding on the perception of breast cancer for women at risk of breast
cancer. Specifically, the proposed study will examine the woman’s biological reaction with
respect to a breast cancer related stressor, a discussion of breast cancer risk between the woman
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and her daughter. The effects of this potentially stressful interaction on the activation of the
HPA and SAM axes will be evaluated in relation to other anxiety and worry variables.
Research Questions
1. What is the relationship between the mothers’ biological stress response and their
general level of anxiety? The hypothesis is that women who experience increased overall anxiety
will also show an increased biological response because of an over activated stress response
system.
2. What is the relationship between the mothers’ biological stress response and breast
cancer specific concern? As seen in previous studies (Gold et al. 2003, James et al. 2004) women
at increased risk for breast cancer have elevated responses to stressors. It is hypothesized that
women with increased breast cancer concern will also have an increased stress response. For
women who are more concerned about breast cancer, experiencing a breast cancer specific
stressor will incur a larger stress reaction from their systems.
3. What is the relationship between the mothers’ biological stress response and their
perceived breast cancer risk? Similarly as with concern, it is hypothesized that women, who
perceived their risk to be higher, will also have increased biological stress response to the task,
which will appear in their cortisol and alpha-amylase levels.
4. What is the relationship between the mother’s biological stress response and their
observed anxiety and avoidance behavior during the breast cancer discussion? If a person is
showing anxiety and distress, it would be expected that the stress will also be detected in a
physiological measure. The hypothesis therefore is that women who show more anxiety and/or
avoidance during the interaction will also show an increased biological stress response in their
cortisol and alpha-amylase levels.
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METHOD
Participants
This study included a total of 58 mothers with ages ranging ranged from 32 to 60 years of
age with a mean of 48 and a standard deviation of 6.3. The mothers participated in the task with
their daughters, whose age ranged from 11 to 32 years with a mean of 19 and a standard
deviation of 5.6. This particular study however focuses only on the mothers’ data. The number of
years of education for the mothers ranged from 9 to 22 with a mean of 16 years and a standard
deviation of 2.2. Out of the 58 mothers, 33 had been diagnosed with breast cancer. The racial
distribution of the sample based on self-report questions was as follows out of the 58 women: 41
were Caucasian (71%), 11 African American (19%), 2 other (3%), and 4 did not respond (7%).
Measures
Generalized Anxiety. The Beck Anxiety Inventory (BAI) is a widely used measure of
symptoms of anxiety in non-psychiatric samples (Beck, Steer, & Brown, 1996). It is a self-report
questionnaire which asks the participant to respond about their anxiety symptoms experienced in
the past week, such as “unable to relax” and “fear of dying”. The 4-point Likert scale ranges
from 0 (not at all) to 3 (severely, I could barely stand it). It consists of 21 items with higher
scores indicating a greater severity of anxiety. For this study, Cronbach’s alpha was 0.86 which
based on accepted levels presents a very good to excellent reliability.
Avoidance and Intrusive thoughts. The Impact of Events Scale (IES) is a measure used
to assess avoidance and intrusive thoughts with respect to a specific stressful event, in this case,
breast cancer. The IES is a 15-item self-report questionnaire that measures current degree of
impact of the specific stressful event (Horowitz, Wilner, & Alvarez, 1979). Participants were
asked to indicate how frequently each item had been true with respect to breast cancer in the 7
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days preceding the interview. The responses were made on a 4-point scale ranging from not at
all true to often true. The IES is subdivided into two subscales: Avoidance with eight items and a
score range of 0-40 and Intrusion with seven items and a score range of 0-35. Examples for the
Avoidance subscale are “I try to remove it from my memory,” “I try not to talk about it,” and “I
try not to think about it.” Examples for the Intrusion subscale include “I think about it when I
don’t mean to,” and “Pictures about it pop into my mind.” The IES has been widely used in the
psycho-oncology literature as a measure of cancer-related anxiety. Thewes, Meiser, and Hickie,
(2001) suggest good internal consistency (Cronbach’s alpha=0.84–0.91), and satisfactory testretest reliability (IES-Total r=0.80). For this study the Cronbach’s alpha for the IES scale of
avoidance was 0.81 and for intrusion 0.75. These are adequate to good based on accepted values.
Perceived Risk. Because of the lack of an established measure of perceived risk, the
assessment of perceived risk was based on a self-report assessment of risk question. The
participants were asked to respond to the question: “How likely are you to get breast cancer?” on
a four-point Likert scale ranging from 1 very unlikely to 4 very likely.
Physiological stress. Saliva samples were collected once before the mother-daughter
interaction and three times after the breast cancer discussion to analyze levels of cortisol and
alpha-amylase as a measure of norepinephrine. Extensive research has established that salivary
levels of -amylase serve as a reliable proxy for levels of norepinephrine, which cannot be
extracted from saliva (e.g., Chatterton et al., 1996; Skosink et al., 2000). Saliva collection was
chosen for determination of cortisol levels because it is simple, non-aversive to the subject, and
can be collected repeatedly throughout the study.
The saliva samples were obtained with a salivette. Participants were asked to chew on a
piece of cotton for a minute and get as much saliva into it as possible. After this, the cotton was
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then placed back in the salivette. The samples were then stored at 0ºC before being sent off to
Salimetrics at Pennsylvania State University to for analysis. (Details for shipping and method for
conducting assays are available at the website for the laboratory at www.salimetrics.com/testing
services.) These data points would allow for study of reactivity to and recovery from stress. The
discussions were scheduled in the afternoon between the hours of 4 and 6:30pm to control for
diurnal fluctuations in cortisol. The analysis was conducted in duplicate and the mean level of
the two tests was used for the data analyses
Salivary cortisol concentrations are independent of flow rate, and reflect unbound “free”
cortisol levels in plasma. Because the level of cortisol in saliva is lower than level in the
circulation, a standard curve developed to capture the range of values expected in plasma
samples was used. The assays conducted in Dr. Granger’s lab have been designed to specifically
address the following three problems that have been observed in the use of salivary cortisol
analyses. First, the majority of available immunoassays for saliva cortisol are modifications of
protocols developed for the use with serum/plasma. The calibrators used in those assay kits are
suspended in a human serum matrix. Given that the composition of serum is markedly different
from saliva, these calibrators are likely to produce results that are influenced by matrix differences.
To ensure the most accurate results, this salivary immunoassay is designed using a matrix that
matches saliva. Second, the level of cortisol in saliva is significantly lower than levels in the
general circulation. The use of a standard curve developed to capture the range of values expected
in serum/plasma samples is often not sensitive enough to capture the complete range of individual
differences in the level expected in saliva. This assay is designed to capture the full range of
salivary cortisol levels while using only 25 µl of saliva per test. Third, the pH of saliva is easily
lowered or raised by the consumption of food or drink. Performance of immunoassays becomes
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compromised as the pH of samples to be tested drops below 4. This results in artificially inflated
levels. This assay system is designed to be very sensitive to the effects of interference caused by
collection techniques that affect pH. In addition, a built-in pH indicator warns the user of acidic or
basic samples.
Behavioral observation. The communication styles were determined through behavioral
observation of the taped discussion on breast cancer. The observation procedure used was based
on the methods developed by Conger and colleagues in studies of families coping with stress
(Reuter 1995).
The mother-daughter pairs spent 15min discussing their feelings and concerns about
breast cancer. The following were the questions prompting discussion for the issue of
disagreement:
What is the disagreement we seem to have about _______________? When do we have
this disagreement and what usually happens? How do you feel about this issue? What can we do
to solve this problem?
For the breast cancer topic, these were the questions on the card:
What kinds of feelings do we each have about breast cancer and the chance that we might
get breast cancer? How often do we talk about our feelings about breast cancer? If we don’t talk
about it, then why not? What prevents us from talking about it? What is it about breast cancer
that has most affected our lives? What is the most emotional or difficult time in our family
regarding breast cancer? Do we feel that we have any control over the chance of getting breast
cancer?
Mom: Do you worry about your daughter and her risk of breast cancer?
Daughter: Do you worry about your mom and her risk of breast cancer?
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Coding of Mother-Daughter Interactions
Both discussions were videotaped. The Iowa Family Interaction Rating Scales (IFRS,
Melby & Conger 2001) were used as the manual for coding emotion and communication in the
mother-daughter interactions. The IFRS are designed to measure behavioral characteristics of
individuals and the exchange between the two as the pair conveys information both through
verbal and nonverbal communication.
This is a macrosystem with a total of 19 scales. These include 14 general scales to
describe the individual behaviors and characteristics of mothers and daughters: Sadness,
Anxiety, Positive Mood, Externalized Negative, Lecture/Moralize, Whine/Complain, Hostility,
Denial, Warmth/Support, Listener Responsiveness, Communication, Prosocial, Antisocial,
Avoidance; two used for scoring behaviors of the mothers in their relationship with their
daughters: Parental Influence, Sensitive/Child Centered; two for daughters in their relationship
with their mothers: Instrumental Caretaking, Emotional Caretaking; and one as the subjective
opinion of the rater: Rater’s Response.
This analysis focused on Anxiety and Avoidance as two scales that measured the
behavior representative of anxiety and distress associated with discussing the topic of breast
cancer.
Anxiety (AX). The anxiety scale measures how much the participant’s verbal and
nonverbal behaviors communicate emotional distress conveyed as anxiety, nervousness, fear,
tension, stress, worry, concern, and embarrassment. The participant may appear tense, fearful,
uncomfortable, and/or self-conscious. Some examples of anxiety: “I am really concerned about
this” (said with tense voice), “I’m really worried,” and nervous fidgeting.
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Avoidance (AV). The scale measures the extent to which the participant averts her gaze
and/or orients her body (head, arms, shoulder, or torso) away from the other person in such a
manner as to avoid interaction. This avoidant manner conveys rejection, withdrawal, and
evasion of the other person. Examples of Avoidance (italicized):
Mother discloses information about their family history of breast cancer and becomes teary
talking about her own mothers’ battle with the illness in her early 40’s. Daughter turns away and
stares down. Daughter says “I don’t know if it’s that, it’s that I’ve got other things to deal with, I
mean, I don’t NEED another problem to think about…and it’s not like I really need to think
about it”. Mother immediately looks away. Mother says “So how do we usually get off the
topic? What happens”? Daughter frowns, rolls her eyes, looks down and says, “I just say- ‘I
don’t want to talk about it’… “I DON’T care.”
Even though these two scales were the original focus of the study, additional exploratory
analysis also included two other behaviors:
Whine and Complain. This scale assesses the degree the participant demonstrates
dissatisfaction by means of whining and whiny complaining. The expressions convey the sense
the focal is an innocent victim, that things are not fair, and that she has been mistreated or
misunderstood. Note the use of “poor me” tone of voice with a sing-song nasal quality.
Examples: “I never get to go anywhere” and “You are ruining my life”
Positive Mood. This scale measures the degree the participant appears content, happy,
and optimistic and/or demonstrates positive behavior toward self, others or things in general.
Both nonverbal communication such as facial expression and the content of the statements are
taken into account. Examples: “John is a good friend,” and “We can do this!”
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The scales range from 1 (the behavior was not at all characteristic of the person) to nine
(the behavior was extremely characteristic of the person). The ratings were given by observers
trained in the scales and used to derive scores for the mother-daughter pairs on behavioral
dimensions. To become a coder, the person had to work through several steps. First he had to
study the manual with the description and definitions of the scales. Next a test that asked for the
name, definition, and two examples of all the scales had to be passed with a score of 80% or
better. Once the person was familiar with the coding system, he would code interactions
previously coded by reliable coders. The person would be considered a reliable coder when
rating 80-85% of the scales within 2 points of the reliable coders. All the interactions were
coded by two reliable coders. In codes where there was a difference, it was discussed until a
consensus code was decided on for those scales. The consensus codes were used as the data.
Procedures
Recruitment
Participants were recruited through the Vanderbilt Breast Center and at Meharry Medical
College Breast Center. Women seen at the Breast Center were approached about their possible
participation in the study. Interested women were provided with a brochure describing the study
and asked for their permission to be contacted by a member of the research team. Recruitment
brochures were also distributed at Vanderbilt-Ingram Cancer Center events as well as Komen
Foundation, Greater Nashville Affiliate breast cancer risk awareness events. The foundation also
printed announcements on their newsletters. Advertisement through the Medical Center
Communications Office email list distributed an email describing the study to VUMC personnel.
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The women who filled out an information sheet were then contacted by a member of the
staff, explained the experiment, and asked if they would like to participate. If they accepted, they
were asked to schedule an appointment for both mother and daughter to come to the lab.
Questionnaires
Then they were mailed the first set of questionnaires and asked to return them as soon as
possible.
Lab visit
Before the arrival of the participants, the laboratory was set for the experiment: the TVs
and video recorder were set up and the salivettes were labeled with the participants’ ids and the
letters A-E for the sequential gathering of saliva samples. A coin was also flipped to determine
which topic, whether breast cancer or an issue of disagreement, would be discussed first.
The participants were met by one of the investigators and escorted into the lab. The
nature of the study was again described to the participants and they were given the consent forms
to sign unless they had been already returned with the initial questionnaires. The first saliva
sample for baseline reading was collected by asking each person to chew on a cotton ball for
about a minute and then return it to the salivette. Next a short questionnaire the Family Issues
Selection Form was given to the pair to identify from a list of possible issues, one on which they
disagreed. Based on this questionnaire the other topic of discussion was determined.
The mother and daughter were seated beside each other on couches in a small room. The
camcorder was in front of them. Depending on the order established by the coin toss, they were
given a card with discussion questions either on the issue of disagreement or breast cancer.
They were asked to ignore the camera and simply talk to each other as they normally
would. The investigator would leave the room, close the door, and not return until the 15min
Stress Responses 22
were up. After the 15min the investigator would return and give them the second card with the
other discussion topic. The same instructions were given to discuss the topic for 15min. The
investigator would again leave and return after 15min. Upon return a second saliva sample was
taken on both mother and daughter and a timer started. The mother was taken to a separate area
for the recovery period. Both mother and daughter were asked to watch a relaxing video on
nature called “Denali”. Saliva samples on each were taken again 15 and 30min later.
Following the interaction, a research assistant administered a semi-structured interview to
the daughters. While daughters participated in the interview, the mothers were given the BDI-II,
BAI, and either the CBCL or the YABCL to complete. Upon the daughters’ completion of the
semi-structured interviews, mothers were privately interviewed by the research assistant while
their daughters complete either the YASR or the YAR depending on their ages.
Once they were finished, they were debriefed and asked what the experience was like for
them and given check request forms. The mother-daughter pairs were each paid $10 for an initial
questionnaire, $15 for the experiment, and $10 for a follow-up questionnaire. The salivettes were
then taken to a freezer for storage. Six months later, follow-up questionnaires were mailed to the
pair.
RESULTS
Descriptive Statistics
Mean and standard deviations for all variables are presented in Table I. The means and
standard deviations show there is enough variability within the data to carry out analyses to test
the research questions and hypotheses. The standard deviations for the cortisol measurements
however are larger than the means. This indicated the data is skewed toward 0 showing a lack of
sensitivity of the measurement or a lack of sympathetic arousal in the task.
Stress Responses 23
The mean of the BAI scores for the women is within the range of normal anxiety
according to Beck and Sterr (1990). For the IES, the intrusion and avoidance scores are lower
than women newly diagnosed with breast cancer (Epping-Jordan, Compas, & Howell, 1994).
Perceived risk cannot be compared to normative samples, but the average of 2.85 means most
women saw their risk as somewhat likely. The levels of cortisol were quite low in comparison to
standard laboratory stress test such as the Trier Stress Test levels of 10-15µg/dL reported in the
literature. The levels of alpha-amylase seem comparable to standard laboratory stressor results.
Research Question 1: Stress Biology and General Anxiety
The relationship between stress biology and general levels of anxiety was tested by
analyzing the correlations between salivary cortisol and alpha-amylase and BAI scores. As
presented in Table II, a significant correlation was not found between BAI and cortisol (r = .09 to
.24). For alpha-amylase, the first time point was significantly correlated r= .39 at p<0.05. The
correlations of alpha-amylase for the last 4 time points (r= -.09 to .21) were not significantly
correlated with BAI scores. Alpha-amylase is significantly correlated with itself as shown in
Table III (r =.56 to 0.85; p < 0.01). Table III also shows that alpha-amylase and cortisol are not
significantly correlated with each other except at alpha-amylase 3 with cortisol 3, 4, and 5 (r =
.36 to .42; p < 0.05). Except for the one significant result of alpha-amylase 1, the results were
contrary to the initial hypothesis.
Research Question 2: Stress Biology and Breast Cancer Specific Worries
To study the relationship between stress biology and worries and concern about breast
cancer, the correlations between salivary cortisol and alpha-amylase and IES avoidance and
intrusion scales were tested. The results are presented in Table II. There was no significant
correlation shown between alpha-amylase and either IES scale (with IES avoidance r = -.24 to
Stress Responses 24
.01; with IES intrusion r = -.01to 0.34). No significant correlation was found between cortisol
and IES avoidance (r = 0.09 to 0.24). However, a significant correlation (r = 0.49 to .57) was
found between cortisol and IES intrusion scale, with p < 0.01 for all five time points. It is not
surprising that all five time points would be significant since, as Table III shows, cortisol was
significantly correlated at the five time points (r = .91 to 0.98, p < 0.01). It was predicted that
both stress biology markers would correlate with both scales of the IES. However, this was not
the case and only IES-intrusion and cortisol levels were significantly correlated.
Research Question 3: Stress Biology and Perceived Risk for Breast Cancer
The relationship between stress biology and perceived breast cancer risk was tested by
analysis of the correlation between alpha-amylase and cortisol levels with the perceived risk
score. As Table II shows, a significant correlation was only found between cortisol measurement
at time 1 and the perceived risk score (r= -.64; p < 0.05). These results contradicted the
expectation that the perception of risk would affect the physiological response of the participants.
The results go further against expectations in that the correlation is negative and indicates than
more perceived risk correlates with less cortisol.
Research Question 4: Stress Biology and Observed Maternal Behavior
For further study of stress biology, its relationship with the mothers’ anxiety and
avoidance behaviors during the breast cancer discussion was correlated with their levels of
cortisol and alpha-amylase. Contrary to the hypothesis, no significant correlation was found. The
correlations between alpha-amylase and anxiety ranges were r = -.13 to.10 and avoidance r =
-.10 to .12). For cortisol the correlations with observed anxiety ranged from r = .04 to .18 and
with avoidance r =.15 to.19.
Stress Responses 25
Since no significant results between avoidance and anxiety were found, some exploratory
analysis was carried out because of the large amount of behavioral data that was available from
the coding of the mother-daughter interaction. Correlations between the sixteen codes for the
mothers and cortisol were carried out to view if any of the observed behaviors were significantly
correlated. Whine/Complain was significantly correlated with r = .65 to .75; p < 0.001. Positive
mood was also significantly correlated r = -.39 to -.49, p < 0.03. Because of the large number of
correlations carried out, the p value was decreased to 0.003 for a correlation to be considered
significant. With the stricter requirements, the whine/complain correlation remained significant
with p < 0.001.
DISCUSSION
Research Question 1: Stress Biology and General Anxiety
General anxiety as measured with the BAI did not show a significant correlation with the
biological stress levels of either stress axis. The results go against the hypothesis that women
with higher general anxiety would also show an increased biological response. The one positive
correlation may indicate that the tests were not sensitive enough, but the biological reactions are
in some way related to general anxiety. This pattern is somewhat different from the findings of
studies by Bovberg and colleagues who found that biological stress responses were related to
general sources of stress in women at risk for breast cancer. To the extent that the BAI reflects
general levels of anxiety and stress, the current study did not replicate the findings of Bovberg.
Research Question 2: Stress Biology and Breast Cancer Specific Worries
On the second research question, a positive correlation was found between cancer
specific worries and cortisol levels. It is important to note that although no correlation was found
between general anxiety levels and biological stress responses, there was a significant correlation
Stress Responses 26
for cancer specific worries. It is an interesting finding that only the HPA axis and not the SAM
axis (as reflected in levels of alpha amylase) showed a corresponding reaction during the task
with respect to the scores on intrusive thoughts of the IES.
Previous research has found avoidance to be associated with poorer outcome in cancer
patients (Epping-Jordan, Compas & Howell, 1994). The reasons mentioned for the negative
outcomes were the non-compliance and non-adherence to treatment associated with the
avoidance. In this study, however, no significant correlation was found between IES avoidance
and cortisol. On the other hand IES- intrusion did show a significant correlation. A reason is that
intrusion could be considered of shorter term effect. Since the IES asks about symptoms in the
past 7 days, women may have been influenced to think about breast cancer because of their
participation in the study. Because the thoughts had just begun, perhaps the participants in the
current study were not yet so bothered by them to try to avoid them.
Research Question 3: Stress Biology and Perceived Risk for Breast Cancer
No significant correlation was found between perceived risk and stress biology. An
explanation for this is that the measure of perceived risk was a single item measure that did not
have reliability. There was also the limitation of sample size because women who had already
had breast cancer were instructed to not fill out the assessment of risk question. This caused a
decrease in the sample size to 13 women, which in turn decreased the power of the analysis.
Another reason for the lack of a significant result however might be that perceived risk is
not a direct measure of worry. Women might believe they are very likely to get breast cancer, yet
not consider it something to worry about which could explain the lack of correspondence
between stress levels and perceived risk levels.
Research Question 4: Stress Biology and Observed Maternal Behavior
Stress Responses 27
Contrary to the original hypotheses, the mothers’ anxiety or avoidance behaviors were
not correlated to either cortisol or alpha-amylase levels. A reason might be that the women are
not even realizing their own sensitivity to the topic of breast cancer and their stress was seen in
their physiological response but not on their physical behavior. The significant correlation
between whine/complain and cortisol levels was an unexpected finding which points to a very
specific behavior and stress biology relationship.
Importance of the Current Study
The findings from this study, point to the importance of breast cancer specific concerns.
It is not only general anxiety that will affect the biological stress response but a more specific
worry and concern related to breast cancer. This is of importance because of the effects of over
activation of the biological stress responses. The evidence in relation to stress and cancer is
confusing and the connection between the two has not been revealed. Nevertheless stress has
great implications with relation to health. In particular chronic stress has damaging effects on the
immune system that decrease the body’s ability to ward off against virus and bacteria making
one more susceptible to contagious diseases.
The relation between cancer and immunosuppression has been proposed as a link to
increased cancer risk via chronic activation of the stress axes. Another possible pathway between
chronic stress and breast cancer is through of a family of proteins, cell transcription factors.
These directly alter the DNA in cell nuclei and can contribute to the development of cancerous
cells. A study by Bierhaus, Wolf, Andrassy, Rohleder, Humpert, Petrov, et al. (2003) suggests
one type of cell transcription factor, Nuclear Factor kappa B (NF-kB), as the mediator that forms
the connection between the stressor and the effects on the body at the cellular level. NF-kB could
Stress Responses 28
be implicated in breast cancer tumor development (Dejardin, Bonizzi, Bellahcene, Castronovo,
Merville, and Bours, 1995).
This study also has implication about dealing with stress. In order to target and attempt
to decrease the stress associated with breast cancer, the focus needs to be on breast cancer
specific issues, not just general anxiety or perceived risk. This offers an option for psychological
intervention in medical treatment. By using the IES, a short measure that reflects breast cancer
specific worries, and has been shown to be related to stress reaction, patients can be screened
without the requirement for a doctor interview. This is an option that could improve treatment
through more comprehensive care.
Limitations and Future Directions
Future studies could be improved in several ways. A larger sample would undoubtedly
make the power of the analysis greater and the effects easier to recognize. Another way would be
to have a more focused breast cancer stress task to elicit stronger stress responses. The
conversation about breast cancer provided an honest sample of behavior but did not elicit much
biological stress reactivity from the participants. By having a breast cancer specific stress task
differences in cortisol and nor-epinephrine (via alpha-amylase) could be better picked up. It
would also be interesting to further the study of the relationship between the whine/complain
behavior and the body’s stress reaction.
Stress Responses 29
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Psychological Corporation.
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(2003). A mechanism converting psychosocial stress into mononuclear cell
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Dejardin, F.E., Bonizzi, G., Bellahcene, A., Castronovo, V., Merville, M.P, & Bours, V.
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Stress Responses 31
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Stress Responses 32
Table I: Mean and Standard Deviations for main measures
Measure
Mean
Standard Deviation
BAI
8.23
6.64
IES avoidance
12.11
7.96
IES instrusion
9.09
6.67
Perceived risk
2.85
.86
Cortisol 1 µg/dL
.25
.46
Cortisol 2
.17
.25
Cortisol 3
.16
.35
Cortisol 4
.17
.33
Cortisol 5
.24
.76
Alpha amylase 1
33.08
28.87
Alpha amylase 2
36.68
33.25
Alpha amylase 3
35.60
31.28
Alpha amylase 4
38.75
34.88
Alpha amylase 5
38.01
36.70
Stress Responses 33
Table II: Correlations for cortisol with general anxiety, intrusive thoughts, perceived risk,
observed behavior
BAI
IES
avoidance
IES
intrusion
Perceived
Risk
Observed
Anxiety
Observed
Avoidance
Cortisol 1
.24
.03
.57**
-.64*
.18
.16
Cortisol 2
.11
.19
.57**
-.39
.08
.15
Cortisol 3
.15
.21
.56**
-.15
.04
.19
Cortisol 4
.09
.09
.50**
-.18
.07
.16
Cortisol 5
.15
.13
.50**
-.15
.08
.17
-amylase 1
.39*
-.12
-.01
-.16
.10
-.10
-amylase 2
.21
.01
.13
.06
-.11
-.04
-amylase 3
-.09
-.15
.34
-.03
.01
.125
-amylase 4
-.17
-.24
.18
.21
-.13
.10
-amylase 5
.08
-.20
.18
.05
-.04
.08
* Correlation is significant at the 0.05 level (2-tailed)
** Correlation is significant at the 0.01 level (2-tailed)
Stress Responses 34
Table III: Correlations of Alpha-amylase (-a) and cortisol (Cort) at five time points
Cort 1
Cort 2
Cort 3
Cort 4
Cort 5
-a 1
-a 2
-a 3
-a 4
Cort 1
---
Cort 2
.96**
---
Cort 3
.92**
.96**
---
Cort 4
.91**
.97**
.92**
---
Cort 5
.93**
.97**
.97**
.98**
---
-a 1
.03
-.29
-.31
-.17
-.16
---
-a 2
.18
.16
.23
.24
.25
.82**
---
-a 3
.31
.33
.42*
.36*
.38*
.62**
.69**
---
-a 4
.10
.12
.18
.16
.17
.56**
.72**
.85**
---
-a 5
.19
.19
.29
.25
.27
.79**
.80**
.85**
.75**
* Correlation is significant at the 0.05 level (2-tailed)
** Correlation is significant at the 0.01 level (2-tailed)
Table IV: Correlations between psychological measures
IES
IES
Perceived
BAI
avoidance
intrusion
Risk
BAI
-IES
--.34*
avoidance
IES
--.32*
.28*
intrusion
Perceived
.12
.08
-.41*
Risk
Observed
.11
.08
.04
Anxiety
Observed
-.07
.08
-.03
Avoidance
* Correlation is significant at the 0.05 level (2-tailed)
Observed
Anxiety
Observed
Avoidance
---.01
---
-.01
.01
---