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Our first inquiry concerns a study that explores statistical associations between psychological responses to breast cancer and survival rates. "Influence of psychological response on survival in breast cancer: A population-based cohort study" by Margaret Watson, J S Haviland, S Greer, J Davidson, and J M Bliss, which appeared late last year in The Lancet (354: 1331-1336), followed nearly 600 women.

In broad terms, the study deals with the general issue of whether the mind - in this case, mental and psychological attitudes can affect the course of disease, in this case breast cancer. At least two findings invite discussion. Contrary to the findings of earlier studies that consistently found that women with a "fighting spirit" response to breast cancer had a reduced risk of relapse and death, the Watson study found no association at all between fighting spirit and survival rates.

On this point, then, the study says that mind does not affect the course of the disease. On the other hand, the study also found that women who displayed helplessness/hopelessness had an increased risk of relapse and death. On this point, then, the mind does seem to matter to cancer. (Women who scored high on a scale measuring hospital anxiety and depression had an increased risk of death from all causes.)

One curious aspect of these divergent findings is that helplessness/hopelessness, which does matter, seems on the surface at least to be an opposite of fighting spirit, which does not matter. Put another way, it appears that while fighting spirit makes no difference, a possible opposite makes things worse.

This is how Watson and colleagues summarize the study in their abstract

Background. The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer.

Methods. 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer  (MAC) scale, the Courtauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis.

The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival.

Findings. At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.24]).

There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55  [1.07-2.25]). There were no significant results found for the category of "fighting spirit."

Interpretation. For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be interpreted with caution.

My reasons for writing a comment stem from a concern that this paper may be used by others to support a common prejudice against the possibility that events in a patient's mind could affect the course of her cancer. Specifically, three conclusions may be drawn:    

1. that "fighting spirit" is not important;   

2. that the nature of a patient's general cognitive and emotional response to her cancer may have very little effect on the biology of the disease;   

3. that there is, therefore, little point in further investigating the possibility of extending survival duration in cancer patients through various kinds of psychological adjunctive therapy.In my view, all three conclusions would be unwarranted.

In my view, all three conclusions would be unwarranted.    

1. "Fighting spirit" is a term often used clinically, but difficult to define. It sounds as if it would refer to patients' motivation to do something to help themselves and to their confidence that they will be able to make a difference. One way of defining it, as Watson and colleagues have done, is with the Mental Adjustment to Cancer questionnaire, developed in the standard way by factor analysis of disparate items followed by a reification of the construct as "Fighting Spirit."

A look at the items is instructive, since many of them do not seem to address what we would commonly think of as aspects of such a quality: "I keep quite busy, so I don't have time to think about it ...," "I don't dwell on my illness," "I count my blessings ..." Other items seem more germane: "I try to fight the illness." My point is that this questionnaire is only one way, and not necessarily a very good way, to assess qualities that might be of importance in prognosis. The authors of the study acknowledge the limitations of the method, and don't try to generalize their conclusions from the use of this instrument, but others may.What else could be done?

Two suggestions. If psychometrics must be used, it would be interesting to try more precisely defined constructs such as Bandura's perceived self-efficacy or outcome expectancy. In our own research on these issues, our thinking is that pencil and paper self-report questionnaires will often fail to capture qualities relevant to survival (although they may usefully assess mood). We have come to favor the collection of verbal data over an extended period of time, followed by qualitative analyses.

One reason for this is that, in a recent randomized controlled trial that we conducted with women with breast cancer who received long-term group therapy (Edmonds et al. 1999), there were no significant changes in mean scores on the Mental Adjustment to Cancer questionnaire (or other instruments), although profound clinical changes were often obvious.   

2. Cross-sectional assessments of patients' cognitive and emotional responses -- that is, assessments, in essence, at a single moment in time, the approach used in this study -- might underestimate the importance of psychological attributes. The reason for saying this derives from the basic cell biology of cancer.

When a cancer is detected, it is already near the end of its life span, and has adapted to the microenvironment within its host. If the person is high in, say, "helplessness/hopelessness," selection of variant cells has ensured that those remaining are well able to survive in a biochemical environment corresponding to this psychological state. Conversely for "low" helplessness/hopelessness patients.

A test of a person's psychological status at a single point in time could be misleading. If the tumors are to be influenced by the psyche via changes in physiology, the aim of the various sorts of psychological or cognitive therapy for cancer patients, this will logically require changes along the pathway from mind to body, to assess which needs multiple estimates.   

3. Following the argument in point (2), if psychotherapy is to affect physical disease, and particularly to influence a longstanding, well-adapted cancer, substantial psychological change may be needed. In testing the effects of such interventions on life span we need again to relate the changes taking place in the psyche of patients to their survival duration.

Findings from research based on the usual cross-sectional protocols do not, therefore, allow us to draw any conclusions about the likely effects of such therapies. Further, if substantial psychological change occurs in only a small proportion of the participants in therapy, which is unfortunately quite usual, randomized controlled trial designs may also be misleading, because the influence of these changes on survival may be "lost" in the group means. To detect them, correlative studies will be required.