No Time to Waste: Avoidant Coping Style Scrambles Circadian Rhythms in Breast Cancer Patients, warned the headline of an article in Clinical Psychiatry News. The article went on to claim
Even in the earliest days following a diagnosis of breast cancer, maladaptive coping styles are associated with a disruption in circadian rhythms –which are proven in metastatic disease to be a prognostic indicator of mortality. The surprising finding… holds potentially profound implications for the timing and tailoring of psychosocial interventions in newly diagnosed patients.
And it invoked psychoneuroimmunology for an authoritative sounding warning to breast cancer patients:
The fact that circadian disruption was significant in a subset of patients a mean 19 [sic] days after diagnosis suggests that there may be no time to waste in identifying and treating potentially maladaptive coping responses that could impact not only their adjustment, but also their prognosis.
Women who are diagnosed with breast cancer, enroll yourself immediately in a stress reduction program or support group, if you want to stem the progression of your disease and prolong your life! If you have metastatic disease, maybe you can blame your “maladaptive coping,” your inept handling of the days and weeks immediately after your diagnosis. Such frightening messages to women who are vulnerable because they have just received their diagnosis should require high standards before being released. This article reeks of hype and distortion, starting with its emotional title, No Time to Waste and “Scrambles Circadian Rhythms,” continuing with claims of “profound implications for the timing of psychosocial interventions,” and ending with an exhortation to breast cancer patients that “early breast cancer patients certainly warrant paying closer attention to coping from Day 1.”
The issue is not just skewered science, because the article contains information that is easily misunderstood without a proper context. Breast cancer patients are urged to take get psychosocial intervention under the threat that if they do not, they are missing an opportunity to control the progression of their disease. This is an example of the irresponsible nonsense that I have been complaining in the past two blogs. There is simply no evidence that psychological interventions can slow progression of cancer or extend life. Claims to the contrary serve to burden cancer patients with an unrealistic responsibility for the outcome of their medical condition. Patients who experience progression to a terminal condition are provided with an irrational sense that they are to blame because they did not take the right steps, namely avail themselves of effective psychological interventions. This article implies that breast cancer patients with an unfavorable course have brought it on themselves by getting too stressed out.
It’s not clear whether journalist Betsy Bates Freed, PsyD. actually interviewed the authors of the study on which the story is based. Media coverage often offers direct quotes that appear to have been obtained directly from authors when they actually come from the scientific article. In this particular case, Freed provides a highly speculative direct quote that “circadian cycles regulate tumor growth” as if it came directly from the mouth of the lead author of the study. For the record, there is some evidence of an association between circadian rhythms and progression of metastatic breast cancer, but it is not clear that it is causal or affects”regulation” or in what direction any causal arrows run. Importantly, such findings have not been replicated with early breast cancer patients.
Clinical Psychiatry News is not some dubious CAM website, but an Elsevier published monthly newspaper with an advisory editorial board with recognizable scientist and clinician psychiatrists. It has largely free web access because of pharmaceutical company support. One has to question what editorial control over content is exerted before releasing articles like No Time to Waste.
A recent cohort studyof hyped and distorted news coverage of clinical trials concluded that distorted press coverage often begins with distortion in the abstracts of the articles reporting the clinical trials, specifically the conclusion sections. Is that what occurred with this coverage of the study?
The conclusion of the abstract that prompted the wild claims reads:
Maladaptive psychological responses to breast cancer diagnosis are associated with disruption of circadian rest/activity rhythms. Given that circadian rhythms regulate tumor growth, we need greater understanding of possible psychosocial effects in cancer related circadian disruption.
This seems to have prompted the journalist’s hype and distortion, although the journalist goes much further. The declaration of “maladaptive psychological responses to breast cancer diagnosis” is suspect. The sample included only 57 presurgical breast cancer patients, and although there is understandably some distress immediately after a diagnosis, there is also a naturally occurring trajectory of substantial reduction in distress over the next few months. Even if it comes as a surprise to them, most breast cancer patients bounce back quite well from a diagnosis, at least in conventional psychological terms. I am skeptical about just how much “maladaptive psychological responses” would be found in such a small sample and how the immediate response of these women could even be considered maladaptive. What might be considered maladaptive if it is chronic and unrelenting can be quite normal as an acute response. But we need to refer to the article to further examine the claims in the abstract. Given such a short period of observation, it is questionable whether these authors obtained enough variation in “maladaptive response” in such a short time of observation to establish any association with circadian rhythms.
The article that prompted this press release had just come out in Annals of Behavioral Medicine and can be accessed through a pay wall here. If you cannot access it through your university library website, you can try e-mailing the senior author at email@example.com and requesting a copy.
Let’s give a close look to the article.
The 57 breast cancer patients studied an average of 19 days after diagnosis were mostly Stage 0 to Stage IIa and only 3 had Stage 4 metastatic breast cancer.
The authors hypothesized they would find
Interrelationships between stress (intrusions) and coping (avoidant coping), circadian disruption (rest/activity and salivary cortisol rhythm), and endocrine activation (cortisol awakening response [CAR], mean saliva cortisol levels). Rest/activity and salivary cortisol rhythms were chosen as circadian disruption measures because of their demonstrated prognostic significance in cancer…
Whoa! It is only in metastatic breast cancer that circadian disruption measures have demonstrated prognostic significance. There is a considerable inferential leap here.
The study involved the women providing four days of data from home: brief self-report psychological data collected each morning, and 12 saliva samples on three consecutive days: at waking, a half-hour after waking, at 4 PM, and immediately before bedtime.
In addition to the saliva samples, circadian rhythm was measured with an actigraph worn on the wrist, a movement recording device that registers body motion. The women wore the device for three days and four nights except for when showering or bathing. To assist in interpretation of the movement data from the actigraph, they recorded each morning in a diary times they got into bed, time they fell asleep, when they woke and the time they got out of bed.
It may seem impressive that the method section reports assessments of maladaptive coping and disrupted rest/activity circadian rhythm as measured by 24-hour autocorrelation coefficients obtained with actigraphy. But let’s take a closer look at these measures. I happen to have done some of the earliest work with coping checklists designed to measure what goes on everyday life. I at first had great enthusiasm for their potential, but grew disillusioned, and much to the dismay of those who were adopting the Ways of Coping Checklist that my group had produced, I wrote an article suggesting it be labeled
Hundreds of studies have established that use of this instrument is unlikely to yield findings of substantive importance and that the risk of confounded and otherwise spurious results is high.
I was really reluctant to disrupt all of the attention that our work was getting, but I decided that coping measures performed that badly and that their brief items really did not give much indication of what was going on people’s lives. The same holds true of the coping measures that came after ours.
I also did some work with actigraphy assessments of prostate cancer patients undergoing androgen deprivation in which I tried to determine if their hot flashes caused sleep disturbance. Actigraphy assessments are basically just a matter of the registering of arm movement or leg movement, if that’s where the device is placed. Making sense of short periods of measurement can be quite difficult, particularly without considerable additional information and if assessments made during waking hours reflect subjects simply sitting or doing sedentary tasks.
Readers who don’t usually wander further into methods and results sections of journal articles might want to skip the next eight paragraphs and get to my conclusion that there is not a lot exciting going on in this article and there is certainly no basis for the outrageous claims in the news article based upon it. However, my whole point is to teach skepticism about psychoneuroimmunology, and it would defeat my purpose if readers uncritically accepted my interpretations. Please, be skeptical of me too.
The particular coping measure used in this study was only six items long and the items are highly ambiguous. The two items for self distraction were “turning to work or other activities to take my mind off things” and “doing something to think about it less, such as going to movies, watching TV, reading, daydreaming, sleeping or shopping. These sound like reasonable strategies. The two items for denial were “saying to myself ‘this isn’t real’” and “refusing to believe it happened,” which certainly could be expected to occur less than three weeks after diagnosis of breast cancer. The two items for behavioral disengagement were “giving up trying to deal with it” and “giving up the attempt to cope.” I am sure that a mentally healthy woman who’s been told she has breast cancer would have times when she endorsed these items. Looking past the authors’ dubious labeling of the scale, none of these items do not seem particularly maladaptive when occurring in the days after diagnosis of breast cancer. There are no norms or established cutpoints for adaptive or maladaptive, and I suspect that the normal range of adjustment after something unsettling like a diagnosis of breast cancer would be quite wide. Bottom line: the authors don’t have a good basis for assuming what they’re measuring is maladaptive and there is no precision to the designation.
The measure of intrusive thoughts was originally developed to assess reactions to stressful events that were already securely in the past. It makes sense to consider high scores maladaptive for a Vietnam War veteran years after he has left the combat zone, but the meaning is much less clear in the immediate aftermath of a diagnosis of breast cancer. But do we make of for instance, of the items “any reminder brought back feelings about it.” Or “I thought about it when I didn’t mean to”? What would be maladaptive for a Vietnam War veteran years later might reflect adaptive deliberation and active problem solving for a woman just diagnosed with breast cancer. Bottom line: I would make too much of the measure of intrusive thoughts. In this study, the scores were actually low for breast cancer patients, but the authors cannot judge the scores representing maladaptive responses with any confidence. What is their proposed cutoff for “maladaptive” and where is the evidence validating it. The measure is sensitive to the normal upset in response to a diagnosis of breast cancer that will mostly resolve over time.
Actigraphy assessment during time in bed basically captures restlessness versus restful sleep and getting up versus remaining in bed. To be confidently interpreted, such assessments need to be accompanied by reports verifying what subjects were doing, including when they went to bed and how long before they fell sleep and whether they got up in the tonight.
Women with newly diagnosed early breast cancer are generally not physically impaired, and so actigraphy assessments of their daytime activity can be highly ambiguous. If they’re not registering much activity, they could be riding in a car, watching movies, relaxing reading a book, or sitting with a couple of coffee, contemplating the news they just received and the implications for their future. Such daytime actigraphy data is more readily interpretable if experimenters have some diary information, just as in actigraphy assessments of time in bed. And keep in mind the impressive designation “24-hour autocorrelation coefficient”is simply a matter of comparing the consistency of rest/activity patterns on the first day to what is obtained at the same time on the second and third days. We have no information as to whether assessment days were weekdays or weekends , and for which women, which can make a big deal of difference.
In contrast, actigraphy assessments of metastatic breast cancer patients register that they are ill. That is one of the problems associated with trying to make sense of the prognostic value of disrupted circadian rhythms It is even more difficult to make comparisons to a sample of women with early breast cancer, most of whom are asleep the majority of the night and out of bed most of their waking hours.
When I go to the Results section of an article, I expect to find simple basic statistics so I can decide for myself what is going on before plunging into complex multivariate statistics for which I depend a lot on the authors’ interpretation. I look for basic correlations. After all the authors are proposing that coping is related to salivary cortisol and actigraphy measures, and they end up taking the position that one can only look at these associations after controlling for income. Why only income? When I couldn’t find basic correlations among key variables, I emailed the senior author and asked her if she could send them to me. She stated that she was on sabbatical, and would send them when she got back. I sent her a message asking if that was a refusal, and she did not reply. I should point out that even if she were on sabbatical, she could certainly have passed on the request to one of her six co-authors who presumably were not so out of touch.
Rather than reporting simple correlations, the authors reported multivariate analyses first controlling for age, cancer stage, and income, before variables like intrusive thoughts or avoidant coping were considered. No associations were found between intrusive thoughts and avoidance on the one hand and salivary cortisol on the other. Given that salivary cortisol was considered a measure of circadian rhythm, this would seem important disconfirmatory result, but little more is said about it. Neither intrusive thoughts nor avoidant coping were related to nighttime restfulness, which also seems surprising. If these women were coping so badly presumably it would disturb the restfulness of their sleep. Avoidant coping and intrusive thoughts were related to how sedentary the women were during the day, and that seems to have influenced the autocorrelation coefficient. But what can we make of this? Some of the avoidant coping items reflect reading, and going to the movies, and I would hesitate to construe has circadian rhythm disruption.
Easily overlooked in these multivariate analyses is that income is as strongly related to circadian rhythm as the coping variables are. I have no idea what to make of this, but it is important not to cherry pick the associations that are consistent with investigators’ hypotheses and avoid those that are troublesome to interpret.
Overall, this article is not transparent in a way that allows independent evaluation of its claims, but is transparent enough to generate some skepticism about any interpretation that women with early breast cancer are hurting themselves by stressing out and not sleeping. Like a lot of psychoneuroimmunology studies, it generates excitement not by its findings, but its claims of relevance to unmeasured things like progression and survival. And it gives a strong sense of confirmatory bias by overlooking predicted associations that were found in highlighting those that were. We are not told enough about the nature or circumstances of measurements, nor are we provided basis statistics, and in the end, we are given no more basis for claiming that disrupted circadian rhythms promote tumor growth in early breast cancer than we started with. There is currently no evidence that disturbed circadian rhythms affect or even predict progression of early breast cancer, and this study only assumed rather than tested this relationship.
I do not blame the authors for the hype and distortions in the Clinical Psychiatry News article. But they could have done a much better job in setting the context of their study, acknowledging the limits of existing research, describing the methods, and reporting their results in ways that did not generate premature claims about clinical relevance or encourage alarm among breast cancer patients. And if they were overcome with enthusiasm about their study, the editor and reviewers at Annals of Behavioral Medicine should have reeled them in.