Date of Award


Document type


Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Seamus Cowman

Second Supervisor

Dr Martina Gooney


Breast Neoplasms, Cluster Analysis, Cytokines


Women with breast cancer experience many symptoms resulting from the primary disease and/ or the treatment of the disease. Psychoneuroimmunology, the theory of sickness behaviour and the action of cytokines may explain why the symptoms of fatigue, pain, depression and sleep disturbances are present and cluster.

This study investigated symptoms, symptom clusters and cytokine activity pre-surgery, post-surgery and post adjuvant treatment using a prospective longitudinal cohort panel design. The study also examined the symptoms for clustering using Hierarchical cluster analysis (HCA). Symptoms were examined in relation to cytokine activity using microarray technology to measure interleukins (1β, 2, 4, 5, 6, 8,10,12,13,17), TNF-a and IFN-y

The final sample comprised of thirty women, ages ranging from 30-77 years. Levels of fatigue, pain and depression differed significantly between the time points. HCA found that the symptoms of fatigue, depression, pain and sleep disturbance formed distinct clusters differing on the level of the symptoms present in the cluster. Although all time points had 4 clusters as the optimal clustering solution, the levels of these symptoms within the clusters were dissimilar across the time points.

Only IL-8 showed a statistically significant difference over time. IL-5 and IL-13 failed to show any relationships to symptoms at any time point. Pain severity was significantly associated with IL-4, IL-6, IL-17, IL-10 and IFN-y. Fatigue was found to be significantly associated with IL-2, IL-4, IL-6 and IL-10. Depression was found to be significantly associated with IL-6, IL-8, IL-10, TNF-a and IFN-y. Sleep disturbance was found to be significantly associated with IL-ip, IL-2, IL-10 and TNF-a. No significant relationships were identified between levels of cytokines and the symptom clusters.

From a clinical perspective, this identification of distinct clusters at time points in the cancer journey is important as it highlights the need for thorough symptom assessment and management to alleviate these symptoms and thus enhance quality of life and levels of functioning. The relationships between symptoms and cytokines in women with breast cancer can be built on in further studies and may lead to the identification of biomarkers for symptoms in the future.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

File Size

19.7 MB


Submitted for the Award of Doctor of Philosophy (PhD) to the Royal College of Surgeons, 2012.