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

Abstract

Purpose The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. Methods Twenty-six patients were recruited, and blood samples were taken pre-and post-NAC. 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 and correlated with the pathological response as measured by the Miller-Payne grading system. χ 2 or ANOVA was performed in SPSS 24.0 statistics software for associations. Results 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. Conclusions Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre-and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.

Circulating Tumor Cell Clusters Are Frequently Detected in Women with Early-Stage Breast Cancer

“…In our cohort of EBC patients, the detection of clusters did not correlate with the likelihood of achieving pCR, a finding already reported in the literature for CTCs [ 12 , 30 ]. Moreover, during the course of treatment a trend towards an increase in CTC-clusters rather than a decrease was observed, as also described in another study using ScreenCell ® filters [ 30 ].…”

“…In our cohort of EBC patients, the detection of clusters did not correlate with the likelihood of achieving pCR, a finding already reported in the literature for CTCs [ 12 , 30 ]. Moreover, during the course of treatment a trend towards an increase in CTC-clusters rather than a decrease was observed, as also described in another study using ScreenCell ® filters [ 30 ]. Indeed, only after surgery did we actually observe a decrease in the number of clusters, although a significantly higher number of clusters persisting after surgery was detected in patients with a pathologically non-responding disease (median 3, IQR 1–11.5 vs. 0, IQR 0–1 for non-responders and responders, respectively).…”

“…To investigate the presence of CTC-clusters in our cohort of patients with MBC and EBC, blood samples collected before starting systemic treatment underwent CTC-cluster enrichment by filtration, followed by a marker-independent CTC-cluster identification based on cytomorphological criteria using ScreenCell ® filters ( Figure 2 A). This simplified identification strategy requires only H&E staining rather than immunofluorescence, and it gives reliable results regarding cell malignancy, independently from the expression of specific markers [ 27 , 28 , 29 , 30 ], as we have previously confirmed by CTC-cluster genomic profiling [ 25 ]. At baseline, in EBC patients, one or more CTC-clusters were detected in 26/37 cases (70%), with a median of two clusters per sample (range 0–20) ( Figure 2 B).…”

“…Indeed, here we applied an easy-to-use filtration-based approach to investigate the relevance of CTC-clusters in 37 EBC and in 23 MBC patients. The ScreenCell ® technology was chosen since its validity has already been reported both for single CTCs and for clusters both when identified based on cytomorphological criteria only, [ 29 , 30 ] or based on marker expression [ 36 ].…”

Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

“…The identification and subsequent characterisation of tumour cells that possess distinguishing features, allowing them to leave the primary tumour, journey through the body to a distal organ, and successfully establish a metastatic niche is critical to the understanding of metastatic disease progression [ 8 , 17 , 18 ]. Cancer cells within the circulation are known as circulating tumour cells (CTCs) [ 19 ].…”