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Psychosomatic Medicine 64:612-620 (2002)
© 2002 American Psychosomatic Society

ORIGINAL ARTICLES

Trait Anxiety and Tamoxifen Effects on Bone Mineral Density and Sex Hormone- Binding Globulin

Linda D. Cameron, PhD, Howard Leventhal, PhD, Richard R. Love, MD and Linda J. Patrick-Miller, PhD

From the Department of Psychology (L.D.C.), Faculty of Science, University of Auckland, Auckland, New Zealand; Rutgers—The State University of New Jersey (H.L., L.J.P-M.), New Brunswick, New Jersey; and University of Wisconsin (R.R.L.), Madison, Wisconsin.

Address reprint requests to: Linda D. Cameron, Department of Psychology, Faculty of Science (Tamaki Campus), The University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: L.cameron{at}auckland.ac.nz


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: Tamoxifen therapy preserves BMD of the lumbar spine and increases levels of SHBG. We assessed whether trait anxiety, a factor linked with a reactive endocrine system, is associated with differential changes in BMD and SHBG levels in response to tamoxifen therapy.

METHODS: Postmenopausal women (N= 140) with axillary-node-negative breast cancer participated in a 2-year randomized, double-blind, placebo-controlled trial of tamoxifen (10 mg twice a day). Levels of BMD and SHBG were assessed at baseline and at 3, 6, 12, 18, and 24 months.

RESULTS: Trait anxiety predicted tamoxifen-induced changes in lumbar spine BMD; high levels of trait anxiety were associated with significantly greater lumbar spine BMD at 3, 12, and 24 months (p values < .05) for women on tamoxifen therapy. High anxiety also was associated with lower levels of SHBG for women using tamoxifen at 3, 12, 18, and 24 months (p values < .05).

CONCLUSIONS: Trait anxiety is associated with greater preservation of lumbar spine BMD in response to tamoxifen and with a suppression of tamoxifen-induced increases in SHBG. Trait anxiety and other affective traits may serve as indicators of underlying physiological processes that moderate the effects of estrogen receptor modulators (such as tamoxifen) in clinical trials. Such data may help to elucidate the physiological mechanisms responsible for some of the variation in individual responses to treatment.

Key Words: trait anxiety • tamoxifen • bone mineral density • sex hormone-binding globulin

Abbreviations: BMD = bone mineral density;; BMI = body mass index;; NSABP P-1 = the National Surgical Adjuvant Breast and Bowel Project P-1;; SERMS = selected estrogen receptor modulators;; SHBG = sex hormone-binding globulin.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
The aim of the present study was to examine the relationships between trait anxiety and physiological reactions to tamoxifen using data from the Wisconsin Tamoxifen Study (1–4), a randomized, controlled trial of tamoxifen therapy for postmenopausal women with breast cancer in remission. The primary goals of this trial were to assess the symptomatic effects and physiological changes induced by tamoxifen and to assess whether these effects were influenced by psychological factors such as trait anxiety. Analyses revealed that tamoxifen increased hot flashes, face flushes, and vaginal irritation (1) and induced other physiological changes, including increases in SHBG (2) and preservation of BMD at the lumbar spine (3, 4).

Our assessments of the role of trait anxiety in the experience of symptomatic side effects revealed that women high in trait anxiety (relative to low-anxiety women) reported greater side effects during the first 6 months of tamoxifen use (5). We concluded that these heightened symptom reports reflected actual experiences rather than anxiety-related tendencies to overreport symptoms for the following reasons. First, participants were unlikely to have known which symptoms were associated with tamoxifen (5); thus, they did not have a bias to focus on hot flashes, face flushes, and vaginal irritation. Second, high-anxiety women did not report increases in symptoms that were unrelated to tamoxifen use. Third, high-anxiety women in the placebo condition did not report increases in either tamoxifen-related symptoms or unrelated symptoms. Although these findings may have arisen because trait anxiety is associated with greater perceptual sensitivity to somatic changes, an alternative hypothesis is that trait anxiety is associated with greater physiological reactions to this hormonal agent. If increased symptom reporting reflects greater physiological responses to tamoxifen, then it also may be associated with differential treatment outcomes, including endocrine responses, changes in BMD, and cancer progression. The present study assesses the hypothesis that trait anxiety is a marker for a physiological substrate that moderates the effects of tamoxifen on lumbar spine BMD and SHBG.

Tamoxifen Therapy: Physiological and Symptomatic Effects
Adjuvant tamoxifen therapy has been found to prolong both disease-free and overall survival in women with breast cancer (6) and to reduce the incidence of new breast cancers in high-risk women by 50% over a 5-year period (7). The Wisconsin Tamoxifen Study findings in which tamoxifen increases SHBG and preservation of lumbar spine BMD in postmenopausal women are consistent with those obtained in other studies (8–10). These BMD changes may be associated with reductions in fractures of the hip, spine, and lower (Colles’) radius (7), although these effects are not well established. The observed symptomatic side effects of tamoxifen also have been identified by other research teams (7, 11), and these adverse reactions have been cited as primary reasons for patient-initiated treatment cessation. In the NSABP P-1 study, for example, 30% of the tamoxifen users who dropped treatment cited hot flashes and other adverse symptoms as the reason (11).

As is the case in most clinical trials of drug regimens, the emphasis to date has been on the average (mean) effects of tamoxifen. The physiological and symptomatic responses to tamoxifen vary considerably, however, with some patients experiencing no changes and others exhibiting high-grade responses. This substantial interindividual variability may partially account for the conflicting evidence regarding the effects of tamoxifen on BMD (3, 9, 12–17) and endocrine levels (18–24). Efforts to identify factors that moderate the effects of tamoxifen on symptoms and physiological outcomes should improve our understanding of the pathways underlying tamoxifen’s effects on tumor progression, SHBG, and BMD (15). Such knowledge also may improve predictions as to who will respond well to tamoxifen therapy and who will be at increased risk for adverse consequences. Although physiological factors such as tumor characteristics (25) and menopausal status (26, 27) account for some interindividual variation, recent advances in psychoneuroendocrinology suggest that emotional factors such as anxiety may correspond to differences in endocrine balances (28, 29) that modify physiological responses to hormonal agents.

Trait Anxiety and Physiological Responses to Tamoxifen
Trait anxiety, identified as a dispositional tendency to experience feelings of worry and fear, is associated with a distinctive pattern of cognitive, emotional, behavioral, and physiological characteristics. The cognitive substrate includes negative self-evaluations (30) and expectations of threatening events (31, 32); the emotional substrate involves tendencies to experience distress, tension, and worry (32, 33); the behavioral substrate includes tendencies such as avoidance of stressful events (34); and the physiological substrate includes increased locus coeruleus/noradrenergic activity (28, 32, 35, 36), as indicated by longer heart rate recovery following stress (37), lower heart period variability (38), and chronically elevated levels of norepinephrine (39), ambulatory blood pressure (40), and forearm bloodflow (41).

Self-report measures of trait anxiety reflect the respondents’ descriptions of their anxiety experiences, which are based on reactions occurring within all four substrates. Given the potential interactions between estrogens and locus coreruleus/noradrenergic activity, it is conceivable that the physiological substrate underlying trait anxiety may respond differentially to a hormonal agent such as tamoxifen. Moreover, the cognitive, emotional, and behavioral substrates of trait anxiety may be associated with potential threats to adherence with tamoxifen treatment. Highly anxious women may be more likely to interpret symptomatic changes as adverse (5), respond with greater distress, and withdraw from treatment. These responses, if sufficiently extreme, may offset any enhancement of tamoxifen’s beneficial effects associated with trait anxiety. The analyses reported here tested the hypothesis that self-reported trait anxiety is an indicator of an underlying physiological system that moderates the hormonal effects of tamoxifen. We predicted that trait anxiety would be associated with differential changes in lumbar spine BMD and SHBG (markers of endocrine changes) among women receiving tamoxifen. We also tested the hypothesis that trait anxiety is associated with poorer adherence and higher attrition in this tamoxifen trial.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Participants
The details of recruitment, eligibility criteria, participant characteristics, and study design have been reported previously (2, 3). In brief, under a University of Wisconsin Human Subjects Committee-approved protocol and with written informed consent, 140 postmenopausal women were recruited to participate in a 2-year, randomized, double-blind, placebo-controlled trial to evaluate the physiological effects and toxicity of tamoxifen therapy over a 24-month period. Participants were screened to verify that they met the criteria for study entry, including a) age of less than 65 years; b) histopathologically confirmed axillary-node-negative breast cancer treated within the previous 10 years; c) postmenopausal status, defined either by the absence of menstrual periods in the preceding 12 months or else by prior hysterectomy and age of 50 years or older; d) absence of clinical evidence of recurrent breast cancer; e) no history of other major medical illness, current systemic therapy for cancer, or use of any hormonal or bone-preserving drugs; and f) BMD in the lumbar spine and radius greater than 80% of values in age-matched, normal women.

The participants, all white, were 46 to 64 years old (mean = 58.12, SD = 4.23) and most were married (83%; 6% single, 6% divorced, 4% widowed). Income levels were in the moderate to high range, with 60% of the participants reporting annual incomes of $30,000 or more. Most participants had a high school degree (78%); 23% had a college degree or higher.

Procedure
Participants were randomly assigned to either a 10-mg tamoxifen or a placebo pill condition. Pills were to be taken twice daily for 24 months. Participants completed self-report measures of trait anxiety and symptoms at a baseline clinic visit and measures of symptoms and pill adherence at 3- , 6- , 12- , 18- , and 24-month follow-up clinic visits. Laboratory assays of lumbar spine BMD and SHBG were taken at all six clinic visits.

Measures
Trait anxiety.
Trait anxiety was assessed by the general anxiety subscale of the Multiple Affect Adjective Check List (42). This measure includes 21 anxiety-related adjectives, 11 of which indicate the presence of anxiety (anxiety-plus items, such as afraid, nervous, tense, and worrying) and 10 of which indicate the absence of anxiety (anxiety-minus items, such as calm, contented, pleasant, and steady). Participants were instructed to "check the boxes by the words which describe how you generally feel." Anxiety scores are calculated by adding the number of anxiety-plus items checked to the number of anxiety-minus items not checked. This trait anxiety measure exhibits satisfactory levels of convergent validity, internal consistency, and test-retest reliability (33). Normative values of mean = 5.46 and SD = 3.44 have been identified using data obtained from 434 university and nursing students (33).

Adherence reports.
The number of pills missed during the previous 2 weeks was calculated based on responses to the following items. First, participants completed a chart to indicate the days and times (AM or PM) of the pills not taken during the previous week. Second, participants were instructed to consider the week before the previous week and respond to the items, "On how many days did you forget to take both of the pills?" and "On how many days during the week before this past week did you forget to take one of your pills?" Responses to both items ranged from 0 to 7 days.

Lumbar spine BMD.
Details of the bone densitometry have been reported previously (3). Area density is defined as bone mass (in grams) divided by the total area of bone (in square centimeters) within the assessed region. The precision of the measurements at the lumbar spine is indicated by the 2% variance around the regression lines for participants.

Serum SHBG levels.
Levels of SHBG (pmol/ml) were determined by radioimmunoassay methods described in previous reports (8, 43).

Tamoxifen-related symptom reports.
The 15 symptoms measured included three that have been identified as exacerbated by tamoxifen: hot flashes; flushed face; and vaginal discharge, irritation, or irregular bleeding (1). Participants were asked to indicate how disruptive the worst occurrence of each symptom had been during the past week using a scale ranging from 0 (didn’t have it) to 10 (couldn’t do a thing because of it). The three symptom ratings were summed to generate scores ranging from 0 to 30.

Statistical Analyses
Following recommended strategies for assessing categorical-by-continuous variable interactions (44), a series of hierarchical regressions assessed the main and interaction effects of tamoxifen and trait anxiety on each physiological variable at each of the six assessments during the 24-month trial. The following variables were added sequentially to the regression model: 1) age and BMI as covariates (if they significantly predicted the outcome measure); 2) baseline levels of the physiological measure (for the follow-up assessments); 3) tamoxifen (vs. placebo) and trait anxiety; and 4) the tamoxifen x trait anxiety interaction term (assessing whether the tamoxifen effect varies by level of trait anxiety). Preliminary analyses revealed that the tamoxifen and anxiety effects on the dependent variables were independent of the following variables: aerobic exercise, cigarette smoking, sleep quantity, state anxiety, depression (trait or state), and hostility (trait or state). These variables, therefore, were not included as covariates in the final analyses. Each hierarchical regression analysis included all patients who were on trial at that particular assessment. The number of women included in the analysis for each of the six assessments (baseline through 24 months) was 70, 69, 66, 64, 62, and 58 in the placebo group and 70, 66, 64, 60, 59, and 59 in the tamoxifen group.

Pearson correlations were used to evaluate a) linear relationships among the baseline variables and b) linear relationships between reports of tamoxifen-related symptoms and the measures of lumbar spine BMD and SHBG at the baseline and follow-up assessments. Independent sample t test was used to test the hypothesis that the group of women who dropped out of the trial because of adverse reactions had higher trait anxiety levels in relation to the other participants.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Adherence and Attrition
Reported adherence to the drug protocol was very high. The proportion of participants reporting consumption of 90% of their pills (missing no more than two pills during the previous 2 weeks) was 95% at 3 months, 90% at 6 and 12 months, 93% at 18 months, and 85% at 24 months. Only one participant (a tamoxifen user) reported adhering to less than 80% of the regimen; she reported taking an average of 68% of the pills. The adherence rates were equivalent in the tamoxifen and placebo groups, and they were not associated with trait anxiety. Serological assessment of tamoxifen and its major metabolites confirmed that more than 95% of tamoxifen recipients had independent evidence of recent drug use (2).

Of the 140 women who entered into the trial, 118 (84%) completed the 2-year drug protocol. Participants went off-study due to recurrence of breast cancer (five placebo and two tamoxifen recipients); adverse, symptomatic reactions (four placebo and five tamoxifen recipients); difficulties traveling to the clinic (two placebo and two tamoxifen recipients); or change of mind (two tamoxifen recipients). One placebo recipient completed the drug protocol but did not attend the 24-month clinic visit. The patients who dropped out of the study did not differ from the overall sample on any of the baseline psychological or physiological measures, with one exception: As predicted, the 10 women who dropped out due to adverse reactions had higher (baseline) trait anxiety scores relative to the rest of the sample (mean = 5.78 vs. mean = 3.32, t(138) = 2.21, p< .03.

Assessments of Baseline Measures
Scores of trait anxiety were generally lower (mean = 3.47) but of comparable variability (SD = 3.26) relative to normative values established with samples of university and nursing students (42). Baseline assessments of lumbar BMD (mean = 1.14 kg/cm2, SD = 0.15) all were 80% or more of values in age-matched normal women. Baseline SHBG levels (mean = 46.33 pmol/ml, SD = 25.42) were comparable with those reported for postmenopausal breast cancer patients in prior studies, in which means ranged from 42 to 60 (14, 22, 45). Correlation analyses revealed no significant associations between trait anxiety, age, lumbar spine BMD, or SHBG; BMI (mean = 26.89, SD = 5.25) was associated with higher lumbar spine BMD (r= .46, p< .01) and lower SHBG levels (r= -.26, p< .01).

Trait Anxiety Effects on Lumbar Spine BMD and SHBG Responses to Tamoxifen
Lumbar spine BMD.
BMI and age significantly predicted lumbar spine BMD at three or more timepoints, and so both were included as covariates in the hierarchical regression analyses. The final models containing all predictor variables are presented in Table 1. Neither trait anxiety nor tamoxifen group assignment was associated with lumbar spine BMD at baseline. Step 3 of the hierarchical regression analysis revealed that tamoxifen use was associated with greater lumbar spine BMD at 12 months (B= 0.0006, SE B = 0.001, t[117] = 2.55, p< .02, R2 change = .005), 18 months (B= 0.0009, SE B= 0.002, t[114] = 2.04, p< .05, R2 change = .01), and 24 months (B= 0.0303, SE B= 0.011, t[110] = 2.75, p< .01, R2 change = 0.01), but these main effects were not significant when the anxiety x tamoxifen interaction term was entered into the models (in step 4; see Table 1). This interaction effect was statistically significant at 3, 12, and 24 months; at each of these timepoints, the preservation effects of tamoxifen on lumbar spine BMD increased with higher levels of trait anxiety. This pattern is illustrated in Figure 1, which graphs the regression results from the 24-month assessment. Although the anxiety x tamoxifen interaction at 18 months was in the same direction, it failed to reach statistical significance (p< .11).


View this table:
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  		Table 1. Tamoxifen and Trait Anxiety Effects on Lumbar Spine BMDa
 


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  		Fig. 1. Relationship between BMD of the lumber spine assessed at 24 months post-baseline and trait anxiety (assessed at baseline) for women receiving 10 mg of tamoxifen (N = 59) and women receiving placebo (N= 58) twice daily for a 24-month period. The linear functions are estimated values based on hierarchical regression analyses of the data provided by the participants in this randomized trial, all of whom had breast cancer in remission.

 
SHBG changes.
Although BMI significantly predicted SHBG levels at baseline, it was dropped from the final regression models predicting follow-up SHBG levels because it was no longer significant when baseline SHBG was controlled. Neither the main nor the interaction effects of trait anxiety and tamoxifen group assignment were significant at baseline (Table 2). At each of the follow-up assessments, tamoxifen use was associated with significantly higher SHBG levels. Significant trait anxiety x tamoxifen interaction effects at four of the five follow-up assessments revealed that high trait anxiety buffered the tamoxifen-induced increments in SHBG; relative to low trait anxious women, high trait anxious women showed smaller increases in SHBG in response to tamoxifen. This pattern is illustrated in Figure 2, which graphs the regression results from the 24-month assessment of SHBG levels.


View this table:
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[in a new window]
  		Table 2. Tamoxifen and Trait Anxiety Effects on SHBG Levelsa
 


View larger version (11K):
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[in a new window]
  		Fig. 2. Relationship between SHBG assessed at 24 months post-baseline and trait anxiety (assessed at baseline) for women receiving 10 mg of tamoxifen (N= 59) and women receiving placebo (N= 58) twice daily for a 24-month period. The linear functions are estimated values based on hierarchical regression analyses of the data provided by the participants in this randomized trial, all of whom had breast cancer in remission.

 
Correlations of Tamoxifen-Related Symptom Reports With Lumbar Spine BMD and SHBG
In an earlier report, we presented evidence that trait anxiety is associated with reports of more extreme experiences of hot flashes, face flushes, and vaginal symptoms in response to tamoxifen (5). To explore whether there are any linear associations between these tamoxifen-related symptom reports and lumbar spine BMD and SHBG, we assessed the correlations among these variables at each of the study timepoints. There were no significant correlations of either lumbar spine BMD or SHBG with reports of tamoxifen symptom at any of the six timepoints; this was the case when correlation analyses included all participants as well as when they included only the tamoxifen participants.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
The data indicate that tamoxifen produced greater preservation of lumbar spine BMD in trait anxious women, suggesting that trait anxiety is an indicator of a physiological substrate that amplifies this estrogen-agonist effect of tamoxifen. In fact, tamoxifen was associated with greater lumbar spine BMD at 3, 12, and 24 months primarily for women reporting relatively high anxiety (at 18 months, tamoxifen use was associated with higher lumbar spine BMD regardless of anxiety level). The absence of significant interaction effects of tamoxifen and trait anxiety on lumbar spine BMD at 6 and 18 months may be due to insufficient statistical power to consistently detect these changes in BMD or else to a lack of stability in these changes over time. The small (albeit statistically reliable) effects of tamoxifen and anxiety are delimited by the small changes in BMD over 3- to 24-month periods, although emerging evidence regarding tamoxifen effects on fractures (7) indicates that these effects are of potential clinical significance. Further research with larger samples is needed in order to gain better clarity on the patterns of anxiety-related influences on BMD responses to tamoxifen over time.

Trait anxiety also was associated with a suppression of tamoxifen-induced increases in SHBG. Although tamoxifen significantly increased SHBG levels regardless of anxiety level, women high in trait anxiety (vs. those low in trait anxiety) exhibited smaller changes in SHBG at all but one of the follow-up assessments.

Although the modest interaction effects of tamoxifen and trait anxiety on BMD and SHBG raise questions of their clinical importance, four considerations suggest that they are of scientific importance. First, these relationships provide clues of indicators for selecting subjects for studies exploring how tamoxifen and other SERMS influence biochemical outcomes. Self-reported trait anxiety appears to be associated with a physiological system that buffers estrogen-related activity of tamoxifen in the liver, where SHBG is synthesized, and enhances tamoxifen’s presumably direct effects on trabecular bone. Because the mechanisms by which tamoxifen influences bone preservation and SHBG synthesis are not well understood, future explorations of these effects may benefit from contrasting subjects who score high and low on measures of trait anxiety and locus coeruleus/noradrenergic activity.

Second, the findings provide new evidence regarding the neuroendocrine processes underlying trait anxiety and suggest that they interact with estrogenic agents in ways that influence such outcomes as SHBG and lumbar BMD. The BMD findings complement evidence of reduced BMD in depressed patients (46–48) and increased levels of bone remodeling markers (osteocalcin, telopeptide, and crosslaps) in depressed women (49). Neuroendocrine substrates underlying affective traits or disorders appear to influence BMD, although the trait anxiety effects are distinctive from those of depression and seem to arise from different patterns of neuroendocrine activity.

Third, the findings suggest that the heightened symptom reports provided by high-anxiety participants (5) at least partly reflect greater responsiveness of their endocrine systems. The greater endocrinological responsiveness of high trait anxious persons may contribute to two general effects: their more frequent experience and increased reporting of psychophysiological symptoms (50, 51) and their reporting of more severe illness symptoms when symptoms are amplified by an immune-induced endocrine response. Observed differences in symptom reporting by trait anxious individuals reflect the reality of their somatic experience and may not simply be a consequence of anxiety-related differences in self-attention and symptom perception. The complexity of the endocrine response is likely to be responsible for the absence of a linear relationship of symptom reports with either SHBG or BMD. Moreover, the factors in the pathway linking tamoxifen to SHBG and BMD may differ from those in the pathway by which tamoxifen affects hot flashes and vaginal irritation.

Finally, the observed relationship between trait anxiety and attrition due to adverse reactions has potentially important implications for tamoxifen treatment and research. Participants who dropped out of the study because of adverse symptoms had higher trait anxiety scores on average, suggesting that potential advantages in bone preservation associated with high anxiety may be balanced by propensities to experience side effects, attribute adverse symptoms to tamoxifen (5), and consequently cease treatment. The excellent adherence and low drop-out rate (particularly in comparison with the NSABP P-1 trial of tamoxifen use by healthy, high-risk women; 11) suggest that women with breast cancer in remission may be particularly motivated to endure the symptomatic side effects. Healthy, at-risk women are likely to be less willing to endure the adverse reactions, and we may expect that women high in trait anxiety may be particularly likely to cease treatment. In a research study, a disproportionate loss of high-anxiety women may lead to muted evidence of tamoxifen’s impact on physiological processes.

We suggest that investigators conducting clinical trials of tamoxifen and other SERMS consider including measures of trait anxiety and its physiological correlates where possible. Data from such trials should increase our understanding of the processes by which these therapies affect physiological outcomes. Larger trials of women with a broader range of medical and demographic characteristics are needed to further elucidate the moderating effects of anxiety on tamoxifen outcomes because the present findings may generalize only to white, postmenopausal women. Moreover, investigators with data from larger trials can examine whether trait anxiety is associated with cancer progression in response to tamoxifen.

The present findings should encourage the measurement of self-reported affective traits as indicators of physiological processes that can influence the effectiveness of hormonal therapies. For example, depression and hostility also are linked with endocrine and behavioral patterns, suggesting that they also may exacerbate or mute responses to hormonal agents. More generally, affective traits can be used as indicators to narrow the focus of research and serve as starting points for analysis. They can suggest hypotheses about trait-linked cognitive processes that affect interpretations of the environment, choices of coping behaviors, and associated physiological reactions; and they also can serve as indicators of underlying physiological mechanisms that may be uncorrelated with cognitive processes (52). As analyses progress and factors underlying the self-reported traits are better understood and more precisely measured, the relevance of the findings for clinical treatment will become clearer.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
This research was supported by Grants PDT302A and PDT302B from the American Cancer Society, by grants from the ICI Pharma Division of ICI Americas, and by a Public Health Service Grant (CA-50243) from the National Cancer Institute.

Received for publication January 23, 2001.

Revision received July 20, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

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