Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics

Introduction: Breast cancers exhibit cellular heterogeneity, containing both stem-like and more differentiated cells. The activity of cancer stem cells (CSC) is likely to be dependent on the microenvironment or niche. Using 158 patient tumour samples, correlations between niche-independent breast CSC activity and clinical and tumour characteristics were tested.Methods: 104 early breast cancer surgical samples and 54 unrelated metastatic samples from pleural or ascitic fluid were harvested. To test CSC activity, isolated cells were grown in both primary (formation) and secondary (self-renewal) mammosphere (MS) culture. Tumour initiating activity was also tested by transplanting breast cancer fragments or cells into the sub-cutaneous flanks of NSG mice (n=84 early and n=10 metastatic).Results: No correlation was found between MS growth, MS formation (%), MS self-renewal (%) or in vivo tumour initiation and breast cancer sub-type, grade, node status or Nottingham prognostic index. 33% of the samples that formed MS in vitro initiated tumours in vivo while only 9% that failed to form MS initiated tumour growth. Metastatic compared to early BC samples grew MS more frequently (53/54 compared to 81/104), and had a higher primary MS formation efficiency (1% vs 0.6%; P