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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.

SUBMITTER: Fornvik D

PROVIDER: S-EPMC6661025 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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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.

Förnvik Daniel D Aaltonen Kristina E KE Chen Yilun Y George Anthony M AM Brueffer Christian C Rigo Robert R Loman Niklas N Saal Lao H LH Rydén Lisa L

Breast cancer research and treatment 20190624 2

<h4>Purpose</h4>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.<h4>Methods</h4>CTCs and ctDNA were analyzed in blood samples collected before and after breast compression in 31 patients with primary breast cancer scheduled for neoad ...[more]

PMID: 31236809

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Project description:Background and aimsThe aim of this study was to characterize circulating tumor cells (CTCs) during neoadjuvant chemotherapy (NACT) in early and locally advanced breast cancer (LABC) patients. Using ultrasound, tumor volume measurement was compared with the presence and the molecular nature of CTCs over multiple time intervals corresponding to treatment periods.MethodsA total of 20 patients diagnosed with breast cancer (BC) of different histotypes were monitored during the NACT period and in the follow-up period (~5 years). Peripheral blood for CTCs (n = 115) was taken prior to NACT, after two to three chemotherapy cycles, after the completion of NACT (before surgery) and at some time points during adjuvant therapy. CTCs were enriched using a size-based filtration method (MetaCell®) capturing viable cells, which enabled vital fluorescence microscopy. A set of tumor-associated (TA) genes and chemoresistance-associated (CA) genes was analyzed by qPCR in the enriched CTC fractions.ResultsThe analysis of tumor volume reduction after administration of anthracyclines (AC) and taxanes (TAX) during NACT showed that AC therapy was responsive in 60% (12/20) of tumors, whereas TAX therapy was responsive in 30% (6/20; n.s.). After NACT, CTCs were still present in 70.5% (12/17) of patients (responders versus non-responders, 61.5% versus 100%; not significant).In triple-negative BC (TNBC) patients (n = 8), tumor volume reduction was observed in 75% cases. CTCs were significantly reduced in 42.9% of all HER2-negative BC patients. In HER2+ tumors, CTC reduction was reported in 16.6% only. Relapses were also more prevalent in the HER2-positive patient group (28.5 versus 66.6%).During NACT, the presence of CTCs (three tests for each patient) identified patients with relapses and indicated significantly shorter progression-free survival (PFS) rates (p = 0.03). Differentiation between progressive disease and non-progressive disease was obtained when the occurrence of excessive expression for CA genes in CTCs was compared (p = 0.024). Absence of tumor volume reduction was also significantly indicative for progressive disease (p = 0.0224).Disseminated CTCs in HER2-negative tumors expressed HER2 in 29% of samples collected during the overall follow-up period (16/55), and in 32% of samples during the follow-up of NACT (10/31). The change accounted for 78.5% of HER2-negative patients (11/14) in total, and 63.6% of the conversion cases occurred during NACT (7/11). For the remaining four patients (36.3%), conversion to HER2+ CTCs occurred later during adjuvant therapy. We believe there is the possibility of preventing further progression by identifying less responsive tumors during NACT using CTC monitoring, which could also be used effectively during adjuvant therapy.

Project description:Understanding the detectability of breast cancer using mammography is important when considering nation-wide screening programmes. Although the role of imaging settings on image quality has been studied extensively, their role in detectability of cancer at a population level is less well studied. We wish to quantify the association between mammographic screening sensitivity and various imaging parameters. Using a novel approach applied to a population-based breast cancer screening cohort, we specifically focus on sensitivity as defined in the classical diagnostic testing literature, as opposed to the screen-detected cancer rate, which is often used as a measure of sensitivity for monitoring and evaluating breast cancer screening. We use a natural history approach to model the presence and size of latent tumors at risk of detection at mammography screening, and the screening sensitivity is modeled as a logistic function of tumor size. With this approach we study the influence of compressed breast thickness, x-ray exposure, and compression pressure, in addition to (percent) breast density, on the screening test sensitivity. When adjusting for all screening parameters in addition to latent tumor size, we find that percent breast density and compressed breast thickness are statistically significant factors for the detectability of breast cancer. A change in breast density from 6.6 to 33.5% (the inter-quartile range) reduced the odds of detection by 61% (95% CI 48-71). Similarly, a change in compressed breast thickness from 46 to 66 mm reduced the odds by 42% (95% CI 21-57). The true sensitivity of mammography, defined as the probability that an examination leads to a positive result if a tumour is present in the breast, is associated with compressed breast thickness after accounting for mammographic density and tumour size. This can be used to guide studies of setups aimed at improving lesion detection. Compressed breast thickness-in addition to breast density-should be considered when assigning complementary screening modalities and personalized screening intervals.

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Dataset Information

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.

Publications

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.

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