Depression: A Lethal Comorbid Factor for Cancer Patients?

July 1, 2011

For women with metastatic or recurrent breast cancer, reductions in depression symptoms over the first year of a randomized controlled trial predicted longer survival times.

For women with metastatic or recurrent breast cancer, reductions in depression symptoms over the first year of a randomized controlled trial predicted longer survival times, reported David Spiegel, MD-an internationally known leader in mind-body medicine.

Speaking at this year’s American Psychiatric Association’s annual meeting in Hawaii, Spiegel described results of a recent study he conducted with Janine Giese-Davis, PhD, and others.1 Dr Spiegel discussed evidence that links depression to cancer, and he shared study results on psychosocial treatments for patients with cancer-particularly those pertaining to survival times.

“Cancer has been converted from a terminal disease to a chronic disease,” said Spiegel, associate chair in the department of psychiatry and behavioral sciences at Stanford University’s School of Medicine. “In 1971, there were 3 million cancer survivors in the US. Now there are more than 12 million. So people are living longer with a life-threatening but not necessarily terminal illness. Consequently, factors that affect survival are becoming increasingly important.”

As reflected in Institute of Medicine reports,2,3 Spiegel said, there is growing recognition that systematic psychological and psychosocial care is a vital part of cancer care.

A 2009 meta-analysis of 31 prospective studies found that after adjusting for prognostic factors, mortality was 25% higher among patients with cancer who had depressive symptoms and 39% higher for those with major depression.4

Ironically, while the public and health care providers understand that depression can worsen the prognosis for those with heart disease, Spiegel said, “they have a much more difficult time understanding that depression with cancer is as lethal a comorbid factor as depression with cardiovascular disease.”

Numerous studies have examined the comorbidity of depression with cancer. Some have indicated that depression may be associated with cancer progression or survival, according to Spiegel. Few survival studies, however, have as-sessed changes in depression.

Study results

Spiegel and his coauthors1 reported on a secondary analysis of a randomized trial involving 125 women with metastatic or recurrent breast cancer. All participants received educational materials and completed a depression symptom measure, the Center for Epidemiologic Studies-Depression Scale (CES-D), at baseline (before random assignment) and at 4, 8, and 12 months. The treatment group received 1 year of supportive-expressive therapy (SET, n = 64), which was not offered to the control group (n = 61).

At baseline and the 3 follow-up points, 101 of the 125 women completed the CES-D. Of the remaining 24, 17 had died or were too ill to complete the questionnaires, 5 had withdrawn from the study, and 2 were busy or no longer interested.

“For the secondary analysis, we looked at the course of depression for the entire sample, but did not report on outcomes based on treatment,” Spiegel added.

The researchers used study data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms would be associated with longer survival.

“We plotted the course of depression over the initial year of the study and then we looked at survival up to 14 years later,” Spiegel said. “Those whose depression was getting worse in the initial year, whether or not they were in the SET arm, died significantly sooner than those whose depression was improving. The mean difference in survival was 2 years, so it was a significant outcome.”

For women with decreasing CES-D scores over 1 year, overall median survival time was 53.6 months (n = 48) compared with 25.1 months for women with increasing scores (n = 53).

Neither demographic nor medical variables associated with survival times, such as age at diagnosis, disease-free interval, or hormone receptor status explained the association, Spiegel reported.

Other studies

There are some 7 randomized trials showing that psychosocial interventions affect survival and 6 others (4 of which involved patients with breast cancer)5 that found no survival benefit for those patients treated with psychotherapy, according to Spiegel.

In 1989, Spiegel and colleagues6 gained international recognition for their clinical trial demonstrating that women with metastatic breast cancer randomized to a year of weekly group therapy lived 18 months longer than control patients. That difference was not accounted for by differences in medical treatment.

A replication study published in 2007 found no overall effect of a similar group therapy intervention on breast cancer survival.7 However, women with estrogen receptor (ER)-negative status assigned to the intervention survived longer than ER-negative controls.

A more recent randomized trial of a psychological intervention for women with early stage breast cancer found significantly reduced rates of relapse and longer survival times compared with the control group.8,9 The intervention included relaxation training, positive ways to cope with stress and cancer-related difficulties (eg, fatigue), and methods to maximize social support, as well as strategies for improving health behaviors and adherence to cancer treatments.

Last summer, Spiegel said, The New England Journal of Medicine published the results of a randomized trial of early palliative care for patients with metastatic non–small-cell lung cancer.10 In the palliative group, attention was given to assessing physical and psychosocial symptoms, setting goals for care, treatment decision making, and coordination of care based on patient needs. Patients who received the palliative care survived longer, experienced lower depression scores, and received less aggressive end-of-life care than did controls.

Spiegel concluded his presentation by explaining that some variance in disease outcomes may come from “host resistance factors,” including response to stress.

“For example, we found among a metastatic breast cancer sample that many women did not have a normal diurnal cortisol pattern,” he said. “That abnormal pattern pre-dicted shorter survival.”

In a recent commentary in JAMA, Spiegel5 described host resistance factors in greater depth and noted: “It is plausible that interventions providing emotional and social support at the end of life have a positive influence on physiological stress-response systems that affect survival. . . . It is not simply mind over matter-but mind matters.”



1. Giese-Davis J, Collie K, Rancourt KM, et al. Decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer: a secondary analysis. J Clin Oncol. 2011;29:413-420.
2. Hewitt M, Greenfield S, Stovall E, eds. Committee on Cancer Survivorship: Improving Care and Quality of Life; National Cancer Board; Institute of Medicine and National Research Council. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2005.
3. Adler NE, Page AEK, eds. Committee on Psychosocial Services to Cancer Patients/Families in a Community Setting; Board on Health Care Services; Institute of Medicine. Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs. Washington, DC: National Academies Press; 2007. Accessed June 1, 2011.
4. Satin JR, Linden W, Phillips MJ. Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer. 2009;115:5349-5361.
5. Spiegel D. Mind matters in cancer survival. JAMA. 2011;305:502-503
6. Spiegel D, Bloom JR, Kraemer HC, Gottheil E. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet. 1989;2:888-891.
7. Spiegel D, Butler LD, Giese-Davis J, et al. Effects of supportive-expressive group therapy on survival of patients with metastatic breast cancer: a randomized prospective trial. Cancer. 2007;110:1130-1138.
8. Andersen BL, Yang HC, Farrar WB, et al. Psychologic intervention improves survival for breast can-cer patients: a randomized clinical trial. Cancer. 2008;113:3450-3458.
9. Andersen BL, Thornton LM, Shapiro CL, et al. Biobehavioral, immune, and health benefits following recurrence for psychological intervention participants [published correction appears in Clin Cancer Res. 2010;16:4490]. Clin Cancer Res. 2010;16:3270-3278.
10. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363:733-742.