A recent long-term follow up study of >50,000 women found no relationship between circulating numbers of CD4+ or CD8+ T-cells and risk of developing breast cancer [45], although it is important to note that this study did not consider T-cell subset composition (e.g. naïve, CM, EM and EMRA) or functionality, which can be altered considerably without greatly affecting total CD4+ or CD8+ T-cell numbers [46–49]. This evidence concerns the gene CD8A and breast cancer.