Detection of circulating tumor cells and circulating tumor DNA before and after mammographic breast compression in a cohort of breast cancer patients scheduled for neoadjuvant treatment

Daniel Förnvik,Christian Brueffer,Niklas Loman,Anthony M George,Lisa Rydén,Robert Rigo,Yilun Chen,Kristina E Aaltonen,Lao H Saal

doi:10.1007/s10549-019-05326-5

Daniel Förnvik, Christian Brueffer + Show 7 more

Open Access

https://doi.org/10.1007/s10549-019-05326-5

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Abstract

PurposeIt is not known if mammographic breast compression of a primary tumor causes shedding of tumor cells into the circulatory system. Little is known about how the detection of circulating biomarkers such as circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) is affected by breast compression intervention.MethodsCTCs and ctDNA were analyzed in blood samples collected before and after breast compression in 31 patients with primary breast cancer scheduled for neoadjuvant therapy. All patients had a central venous access to allow administration of intravenous neoadjuvant chemotherapy, which enabled blood collection from superior vena cava, draining the breasts, in addition to sampling from a peripheral vein.ResultsCTC and ctDNA positivity was seen in 26% and 65% of the patients, respectively. There was a significant increase of ctDNA after breast compression in central blood (p = 0.01), not observed in peripheral testing. No increase related with breast compression was observed for CTC. ctDNA positivity was associated with older age (p = 0.05), and ctDNA increase after breast compression was associated with high Ki67 proliferating tumors (p = 0.04). CTCs were more abundant in central compared to peripheral blood samples (p = 0.04).ConclusionsThere was no significant release of CTCs after mammographic breast compression but more CTCs were present in central compared to peripheral blood. No significant difference between central and peripheral levels of ctDNA was observed. The small average increase in ctDNA after breast compression is unlikely to be clinically relevant. The results give support for mammography as a safe procedure from the point of view of CTC and ctDNA shedding to the blood circulation. The results may have implications for the standardization of sampling procedures for circulating tumor markers.

Highlights

Circulating tumor markers such as circulating tumor cells (CTCs) and circulating tumor DNA can be found in the blood of cancer patients
We have previously investigated if mammographic breast compression in patients with an already present breast tumor could cause shedding of tumor cells to the peripheral circulation [22]
No agreement was found between CTC- and ctDNApositive patients (κ = 0.02, p = 0.92) (A plot of CTC count versus % mutant allele frequency (MAF) can be found in supplementary Fig. S1)

Summary

Introduction

Circulating tumor markers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) can be found in the blood of cancer patients. These markers complement solid biopsies and have the advantage of being physically more accessible and patient-friendly than traditional tissue biopsies. This provides a possibility for prognosis prediction, closer monitoring of treatment response and disease progression, identification of drug targets, as well as an opportunity for early detection of recurrence. The presence of CTCs in the blood of patients with primary breast cancer has been shown to be an independent predictor of decreased disease-free and overall survival [1, 2], but the treatment predictive value of the cells is still under debate [3, 4]. Recent studies have shown that quantification of specific mutations in ctDNA can be associated with early detection of metastases and therapy resistance in breast cancer as well as in other diagnoses [8,9,10,11,12]

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