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

Abstract

Purpose: It 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.

Methods: CTCs 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.

Results: CTC 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).

Conclusions: There 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.

Trial registration: ClinicalTrials.gov NCT02306096.

Keywords: Breast cancer; Breast compression; Circulating tumor DNA; Circulating tumor cells; Mammography; Neoadjuvant.

Conflict of interest statement

YC, AMG, CB, RR, and LHS are shareholders and employees of SAGA Diagnostics AB. LHS has received honorarium from Novartis AG. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1

Examples of CTCs detected with the CellSearch system from a patient in the study

Fig. 2

The number of CTCs found before and after mammographic breast compression in central venous access (a), where two patients are represented by a line going from 0 to 1 CTC and from 1 to 0 CTCs, respectively. The corresponding number of CTCs before and after compression in peripheral blood (b). Figures for mutant allele frequency before and after breast compression in central (c), where two patients are represented by a line from 0 to approximately 0.35, and peripheral (d) plasma, where two patients are represented by a line going from 0 to approximately 0.04 and from approximately 0.03 to 0, respectively. Patients with an increasing value are plotted with red lines, decreasing values in blue, and constant values in green. All patients that did not have any circulating tumor markers are summarized in one line at number/frequency = 0

Fig. 3

CTC (a) and ctDNA (b) detection in central and peripheral sample pairs. In 8/10 CTC-positive pairwise samples, a higher number of CTCs was detected in the central compared to the peripheral blood sample (p = 0.04). In pairwise samples 1–6, no CTCs were found in the peripheral blood sample. In 12/20 ctDNA pairwise samples, a higher mutant allele fraction was found in the peripheral plasma sample (p = 0.50). In pairwise samples 2, 4–7, no ctDNA was detected centrally, and in sample 1, no ctDNA was detected peripherally