The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast-Long-Term Prognostic Significance

Ulrik Narbe, Pär-Ola Bendahl, Kristina Aaltonen, Mårten Fernö, Carina Forsare, Charlotte Levin Tykjær Jørgensen, Anna-Maria Larsson, Lisa Rydén, Ulrik Narbe, Pär-Ola Bendahl, Kristina Aaltonen, Mårten Fernö, Carina Forsare, Charlotte Levin Tykjær Jørgensen, Anna-Maria Larsson, Lisa Rydén

Abstract

Background: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST.

Materials and methods: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS).

Results: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST.

Conclusions: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.

Keywords: CTC cluster; cancer antigen 15-3; circulating tumor cells; invasive ductal carcinoma of no special type; invasive lobular carcinoma.

Conflict of interest statement

The authors declare no personal or professional financial relationship as a conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the study cohort.
Figure 2
Figure 2
Circulating tumor cell (CTC) count at baseline by histopathological type. Abbreviations: ILC, invasive lobular carcinoma; NST, invasive ductal carcinoma of no special type; CTC count, number of CTCs per 7.5 mL blood.
Figure 3
Figure 3
Distribution of CTC counts at baseline and with serial sampling at different time points. Spaghetti plots showing number of CTCs (per 7.5 mL blood) per patient from baseline (BL) to 6 months of follow-up for invasive lobular carcinoma (ILC), left panel (A), and invasive ductal carcinoma of no special type (NST), right panel (B). The p-values correspond to pairwise tests of the null hypothesis of no change in CTC count (Wilcoxon matched-pairs signed-rank test). Note that the scale on the y-axis is logarithmic and that the y-axis has been broken to enable presentation of zeros. A small amount of random noise was added to all zeros to separate the lines. The red line connects the medians at the four time points.
Figure 4
Figure 4
Progression-free survival (PFS) by circulating tumor cell (CTC) count. Kaplan–Meier plots displaying PFS for the invasive lobular carcinoma (ILC) and invasive ductal carcinoma of no special type (NST) subgroups. Cut-off ≥5 CTCs (A–B). Cut-off ≥20 CTCs (C–D). Cut-off ≥80 CTCs (E–F).
Figure 5
Figure 5
Overall survival (OS) by circulating tumor cell count. Kaplan–Meier plots displaying OS for the invasive lobular carcinoma (ILC) and invasive ductal carcinoma of no special type (NST) subgroups. Cut-off ≥5 CTCs (A,B). Cut-off ≥20 CTCs (C,D). Cut-off ≥80 CTCs (E,F).

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