C-Stress project

This project began in 2014 and is ongoing.

Our overall aim is to determine that psychological interventions will improve the response rates to chemotherapy and, potentially, progression free survival of patients with cancer through the reduction of psychological stress.

Breast cancer (BC) is the most common cancer in females, affecting one in eight women. We were the first to report that stress hormones (noradrenaline [NA]) at physiological concentrations induce DNA damage and decrease the efficacy of chemotherapy. In research published in BioMed Central, we stated that psychological stress increases the circulating levels of the stress hormones cortisol and norepinephrine (NE) and that chronic exposure to elevated stress hormones has been linked to a reduced response to chemotherapy through induction of DNA damage. We hypothesized that stress hormone signalling may induce DNA damage through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and interference in DNA repair processes, promoting tumourigenesis.

We need to determine the impact of stress reductions in patients with breast cancer, and establish if stress reduction can affect response to chemotherapy. The data from this study will inform a future trial where stress biomarkers and identification of polymorphisms in the Aberrant Drug-Related Behaviours (ADRB) will allow for a personalised medicine approach for the stratification of patients into mindfulness stress responsive/unresponsive groups and those who are unlikely to benefit from β blockers, and determine if stress reductions improve treatment efficacy.

In addition, the research team was awarded a grant from the cancer charity Team Verrico to examine stress hormone receptors in patients with Triple Negative Breast Cancer (TNBC). Triple Negative Breast Cancer (TNBC) accounts for approximately 20 per cent of all subtypes of breast cancer. Patients with TNBC are treated with standard chemotherapy treatments, and these patients exhibit shorter disease-free survival, a higher rate of relapse and can develop resistance to standard therapies.

Through work with women who have recovered from TNBC, the period of most stress was found to be different for each individual; it may be from the moment of suspicion of breast cancer to the diagnosis, or following diagnosis. Patients experience stress for a variety of reasons: through knowledge that they are high risk, enduring multiple biopsies, indirect stress of family members, as well as fear of pain, sickness and potential end of life. Some patients seek stress interventions such as exercise and positive reinforcement from medically-trained individuals. However, each woman stated that stress was a major factor during their cancer history, and that they felt stress could play a role even in tumour progression and treatment. 

Determining the effects of stress on the efficacy of chemotherapy will have an impact on the potential utility of pharmacological interventions such as beta-blockers, or psychological interventions including mindfulness-based stress reduction, and on the correct time point for administration in the disease trajectory for greatest therapeutic effect. The research will impact patients and clinicians, through recognition that stress is a contributing factor for drug resistance in the treatment of breast cancer.