Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

Abstract

Background: Detection and enumeration of Circulating Tumour Cells (CTCs) has been evaluated in many cancers such as breast cancer. However, the full prognostic and predictive power of CTCs for cancer cannot currently be harnessed, and the association between pathological complete response in patients receiving neoadjuvant chemotherapy for breast cancer and CTCs is still not clear. The aim of this study was to assess if CTCs could be used to predict pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: 26 patients were recruited, and blood samples taken pre- and post-neoadjuvant chemotherapy. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets clusters/microemboli. Counts were then correlated to the pathological response as measured by the Miller-Payne grading system. The associations between CTCs and clusters and pathological variables were evaluated with χ2 or ANOVA tests performed in the SPSS 24.0 statistics software. Results: 89% of the patients had invasive ductal carcinoma and 11% invasive lobular carcinoma. At baseline 85% of patients had CTCs present and only 4 patients were CTC negative. Median baseline CTC count was 7 (0-161) CTCs per 3mls of whole blood. Post chemotherapy, 58% of the patients had an increase in CTCs. This change in CTC count did not correlate with the Miller Payne grade of response to chemotherapy. No significant association was identified between the number of CTCs and clinical characteristics, including patient age, receptor status, tumour grade, disease type, lymph node metastasis, lymphovascular space invasion, radiological response or clinical or pathological stage. However, we did observe a correlation between pre-treatment CTC counts and body mass index, p<0.05. Conclusions: There was no correlation between the pre- and post-chemotherapy total number of CTCs/clusters and the Miller Payne grade. It is not enough to evaluate pathological response for neoadjuvant chemotherapy for breast cancer patients utilising CTCs identified by Giemsa staining alone. Additional characterisation is needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in breast cancer patients undergoing neoadjuvant chemotherapy.