From this large, population-based study, no statistically significant associations were found between psychosocial factors (measured at a median of 11 months after breast cancer diagnosis) and either DDFS or OS when adjusted for known prognostic factors. The observed association from the unadjusted analysis of high scores on the MAC subscale for anxious preoccupation was lost after adjustment for other known prognostic factors. The estimated effects of these established prognostic factors were not influenced by the inclusion of anxious preoccupation in the multivariate model. This suggests that the association of anxious preoccupation with outcome was due to its correlation with poor prognostic factors rather than it directly causing poorer outcomes. That is, younger women with poorer prognosis tumors, in terms of grade and axillary nodal status, were more likely to score high for anxious preoccupation, suggesting that the apparent influence of anxious preoccupation was mediated by these other well-established prognostic factors and their associated treatments (eg, chemotherapy), rather than being independently important.
A strength of this study was its relatively large sample size and length of follow-up, providing adequate statistical power to detect modest relative risks, even for uncommon factors such as depression. Another major strength of our study is that it was population-based, and thus the results are likely to be generalizable to women with disease in the relatively young age ranges studied. The focus on young women is appropriate because, as a group, they have more emotional distress than older women after a breast cancer diagnosis.27
Also, we were able to adjust for a comprehensive range of potentially important prognostic factors, including tumor characteristics, treatment, and host factors (such as age, body mass index, and recency of childbirth).25,26
A potential limitation of our study was the lack of repeated evaluations of the psychosocial factors over time. These factors are dynamic, and previous studies have shown that psychosocial distress is most prevalent in the first few months after diagnosis and then, for the majority of women, returns to premorbid levels after approximately 1 year. We are unable to directly determine from our data whether women who had sustained, rather than transient, psychosocial distress might have been more likely to have worse survival. However, the fact that our questionnaires were not administered at a specific time point after diagnosis but rather over a range of time points (2 to 42 months) could be seen as at least partially mitigating this limitation because we found that adjusting for time between diagnosis and administration of the psychosocial questionnaires produced no substantive changes in the estimates for the association between anxious preoccupation and survival.
Comparison of the current study with much of the literature is difficult because of differences in study design such as study sample characteristics and the timing of measurement of psychosocial factors. Also, because of the wide range of psychosocial measures used in previous studies, even closely related terms derived from different instruments do not necessarily measure the same thing. Two relatively large recent studies used at least some of the same questionnaires as the current study.28,29
A multivariate analysis of one of these, from the Danish Breast Cancer Cooperative Group, also failed to find any association between anxiety and depression (assessed by the HADS 2 months after diagnosis) and survival.28
The other study examined the influence of psychological responses on breast cancer survival using a hospital-based cohort of 578 patients with initially 5 and later 10 years of follow-up.29,30
At 5 years of follow-up, that study found worse overall survival from the adjusted analysis for women who had probable depression (HADS score > 10), with an HR of 3.59 (95% CI, 1.39 to 9.24; P
< .01) and worse event-free survival of women with high (> 12) rather than low scores on the helplessness/hopelessness subscale of the MAC scale (HR = 1.55; 95% CI, 1.07 to 2.25; P
The effect of helplessness/hopelessness was sustained at 10 years of follow-up, but the effect of depression was no longer statistically significant: the authors concluded that “there has been no clear effect of depression on survival as assessed here.”30
In the current study, no association between depression or helplessness/hopelessness and breast cancer outcomes was observed, suggesting that neither of these factors substantially influence breast cancer survival.
Other large studies have not collected the same measures as our study. Hjerl et al, 31
using a retrospective study design, assessed the influence of affective disorders, defined as those necessitating psychiatric hospital admission. They reported that having an affective disorder after diagnosis of early-stage breast cancer was associated with increased mortality. Reynolds et al32
examined coping strategies and breast cancer survival but found no significant associations for women with early-stage breast cancer. Kroenke et al33
studied women with breast cancer in the Nurses Health Study. They showed that socially isolated women had an elevated risk of death owing to breast cancer and all causes, even after adjustment for multiple covariates, although the possibility of residual confounding by socioeconomic status could not be excluded. Tumor stage was adjusted for in the analysis, but early-stage patients and those with metastatic disease at diagnosis were not analyzed separately. This is an important point, because differential effects between patients with nonmetastatic and metastatic disease have been reported by others.32,34
Interestingly, a recent randomized controlled trial of cognitive-existential group therapy designed to improve mood and mental attitude toward cancer in early-stage breast cancer patients did not result in survival benefits.35
This is consistent with the findings of the current study, either because psychosocial factors do not influence survival or alternatively because their impact is so small that a much larger study would be required to show benefit or deficit.
The current study does not support the hypothesis that the measured psychosocial factors influence survival after breast cancer. Psychosocial factors were not associated with large increases in the relative risk of recurrence, although smaller increases in risk (relative risk < 2.0 for depression and fatalism and < 1.5 for the other factors) cannot be excluded on the basis of this study alone. This should be reassuring for women, particularly those who experience substantial levels of psychosocial distress after their diagnosis. It is important to note that this does not negate the potential value of interventions that reduce psychosocial distress in women with breast cancer, as these seem to improve quality of life.36,37