Abstract

Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify beta-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.

Abstract

PURPOSE:

Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival.

METHODS:

In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies-Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival.

RESULTS:

Median survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association.

CONCLUSION:

Decreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis.

Abstract

This paper reviews the evidence for mind-body therapies (eg, relaxation, meditation, imagery, cognitive-behavioral therapy) in the treatment of pain-related medical conditions and suggests directions for future research in these areas. Based on evidence from randomized controlled trials and in many cases, systematic reviews of the literature, the following recommendations can be made: 1) multi-component mind-body approaches that include some combination of stress management, coping skills training, cognitive restructuring and relaxation therapy may be an appropriate adjunctive treatment for chronic low back pain; 2) multimodal mind-body approaches such as cognitive-behavioral therapy, particularly when combined with an educational/informational component, can be an effective adjunct in the management of rheumatoid and osteoarthritis; 3) relaxation and thermal biofeedback may be considered as a treatment for recurrent migraine while relaxation and muscle biofeedback can be an effective adjunct or stand alone therapy for recurrent tension headache; 4) an array of mind-body therapies (eg, imagery, hypnosis, relaxation) when employed pre-surgically, can improve recovery time and reduce pain following surgical procedures; 5) mind-body approaches may be considered as adjunctive therapies to help ameliorate pain during invasive medical procedures.

Abstract

OBJECTIVE:

Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.

METHODS:

A total of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate-vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.

RESULTS:

Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.

CONCLUSIONS:

Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.