Immune responses in primary and metastatic breast cancer

Abstract Breast Cancer is a heterogeneous disease, which affects one in ten women in the UK today. Developments in recent years have led to earlier diagnosis and improved treatments and survival. However, mortality is still high and metastatic disease remains incurable. The role of the immune system in breast cancer has been questioned for over 100 years and more recently has led to major developments most notably in the form of Herceptin. Current evidence suggests that the immune system is stimulated by tumours to manifest a response. Many breast cancers show evidence of this immune response in the form of tumour infiltrating lymphocytes. However contradictory opinions exist as to whether this response is favourable for the host or not. The significance of the findings of many of these studies is limited by several factors, including small patient numbers and the fact that qualitative rather than quantitative assessments of tumour infiltrating lymphocytes have been used. The aims of this study were twofold: Firstly, we set out to develop a practical and efficient method for quantifying immune responses in tissue specimens and secondly, the main aim was to establish the significance of this response, by quantifying the tumour infiltrating lymphocytes in a group of patients with breast cancer, using a well designed study. Our patient group was derived from the Greater Glasgow Health Board database, which was established in 1995 to keep a record of all patients diagnosed with breast cancer in greater Glasgow area. We designed a case-control study to include patients, who were matched on the basis of several factors, recognised as having prognostic significance in breast cancer. The hypothesis to be tested was that metastatic relapse would be less likely in women with breast cancers in which a significant immune infiltrate was present, than in women with cancers in which there was no significant immune-cell infiltrate. We established a reliable and efficient method for immune cell quantification, which will be of value in future studies looking at the immuno-phenotype of the cells that comprise the inflammatory cell infiltrate. Additionally we found that most breast cancers show evidence of an immune cell infiltrate and that this response is likely to be protective