Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

Onstenk, Wendy; Sieuwerts, Anieta M.; Weekhout, Marleen; Mostert, Bianca; Reijm, Esther A.; Deurzen, Carolien H.M. van; Vries, Joan Bolt-de; Peeters, Dieter; Hamberg, Paul; Seynaeve, Caroline; Jager, Agnes; Jongh, Felix E. de; Smid, Marcel; Dirix, Luc; Kehrer, Diederik F.S.; Galen, Anne van; Ramírez-Moreno, Raquel; Kraan, Jaco; Van, Mai; Gratama, Jan W.; Martens, John W.M.; Foekens, John A.; Sleijfer, Stefan

doi:10.1016/j.canlet.2015.03.020

Cited by 41 publications

(38 citation statements)

References 23 publications

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“…Incongruity in ER expression levels had consequences in prognosis. Patients with ER− tumors and ER+ CTCs had longer median time‐to‐treatment, the time between receiving first line of treatment to second line of treatment, compared to patients with ER− tumors and CTCs . These studies showed the potential of liquid biopsy components as a tool for predicting recurrence and prognosis.…”

Section: Utilization Of Liquid Biopsy For Breast Cancer In the Clinicmentioning

confidence: 84%

“…The study concluded that the analysis of TK1 activity level along with CTC count may be used as a potential prognostic, predictive, and monitoring marker to endocrine therapy for these tumor types. 178 180 These studies showed the potential of liquid biopsy components as a tool for predicting recurrence and prognosis. More validation studies are needed to confirm the clinical applications of these non-invasive liquid biopsy methods in predicting prognosis among breast cancer patients.…”

Section: Predicting Recurrence and Prognosis In Breast Cancermentioning

confidence: 99%

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Liquid biopsy in breast cancer: A comprehensive review

2019

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Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell‐free RNA, tumor‐educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.

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Section: Utilization Of Liquid Biopsy For Breast Cancer In the Clinicmentioning

confidence: 84%

Section: Predicting Recurrence and Prognosis In Breast Cancermentioning

confidence: 99%

Liquid biopsy in breast cancer: A comprehensive review

2019

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“…Monitoring CTC over a period of time seems necessary since marker profiles can change during course of a therapy and during disease progression as already shown for ERBB2, ER and PR [27, 32, 59]. For ERBB2, several studies indicated that ERBB2+ MBC patients have EMT-like CTC and that ERBB2 seems to be selectively expressed in cancer stem cells of initially ER+ and ERBB2-negative luminal BC [10, 55].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a multimarker qPCR panel for the molecular characterization of circulating tumor cells in blood samples of metastatic breast cancer patients during the course of palliative treatment

et al. 2016

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BackgroundCirculating tumor cells (CTC) are discussed to be an ideal surrogate marker for individualized treatment in metastatic breast cancer (MBC) since metastatic tissue is often difficult to obtain for repeated analysis. We established a nine gene qPCR panel to characterize the heterogeneous CTC population in MBC patients including epithelial CTC, their receptors (EPCAM, ERBB2, ERBB3, EGFR) CTC in Epithelial-Mesenchymal-Transition [(EMT); PIK3CA, AKT2), stem cell-like CTC (ALDH1) as well as resistant CTC (ERCC1, AURKA] to identify individual therapeutic targets.ResultsAt TP0, at least one marker was detected in 84%, at TP1 in 74% and at TP2 in 79% of the patients, respectively. The expression of ERBB2, ERBB3 and ERCC1 alone or in combination with AURKA was significantly associated with therapy failure. ERBB2 + CTC were only detected in patients not receiving ERBB2 targeted therapies which correlated with no response. Furthermore, patients responding at TP2 had a significantly prolonged overall-survival than patients never responding (p = 0.0090).Patients and Methods2 × 5 ml blood of 62 MBC patients was collected at the time of disease progression (TP0) and at two clinical staging time points (TP1 and TP2) after 8–12 weeks of chemo-, hormone or antibody therapy for the detection of CTC (AdnaTest EMT-2/StemCell Select™, QIAGEN Hannover GmbH, Germany). After pre-amplification, multiplex qPCR was performed. Establishment was performed using various cancer cell lines. PTPRC (Protein tyrosine phosphatase receptor type C) and GAPDH served as controls.ConclusionsMonitoring MBC patients using a multimarker qPCR panel for the characterization of CTC might help to treat patients accordingly in the future.

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“…For this study, 140 patients were retrospectively selected from two prospective clinical trials that have been conducted in six hospitals in the Netherlands and Belgium from 2006 till 2015. Both studies enrolled mBC patients that started with a new line of endocrine therapy or chemotherapy (06–248 and 09–405 study) . Blood for enumeration and molecular characterization of CTCs was collected of all patients before start of this new line of therapy.…”

Section: Methodsmentioning

confidence: 99%

Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer

Kruijff

Sieuwerts

Onstenk

et al. 2019

Intl Journal of Cancer

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The androgen receptor (AR) has potential clinical relevance in metastatic breast cancer (mBC) since it might be a treatment target and has been associated with endocrine resistance. A minimal‐invasive way to determine AR expression on metastatic tumor cells is by characterization of circulating tumor cells (CTCs). Here, we assessed AR mRNA expression in CTCs (CTC‐AR) and in matched primary tumor samples from mBC patients representing different breast cancer subtypes. In addition, we explored CTC‐AR‐status in relation to outcome on endocrine therapy. AR, and 92 AR or estrogen receptor (ER) related genes, were measured in CellSearch‐enriched CTCs from 124 mBC patients and in 52 matched FFPE primary tissues using quantitative reverse‐transcriptase PCR. AR in CTCs was considered positive if the expression was 1 standard deviation higher than the expression measured in 11 healthy blood donors. A total of 31% of the mBC patients had AR‐positive (AR+) CTCs. 58% of the matched CTC and primary tumor samples were discordant with respect to AR status, observing both switches from AR+ to AR‐negative (AR‐) and vice versa. There was no statistically significant difference in progression‐free survival for patients treated with ER‐targeting drugs and CTC‐AR‐status (13 AR+/ 37 AR‐ cases, p = 0.28). Thus, AR can be determined in RNA isolated from CTCs, with in our set 31% AR‐positive samples. Given the discordance between AR status in CTC samples and corresponding primary tumors, determination of AR expression in CTCs might be a promising tool to select mBC patients for AR inhibiting agents.

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Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

Cited by 41 publications

References 23 publications

Liquid biopsy in breast cancer: A comprehensive review

Liquid biopsy in breast cancer: A comprehensive review

Establishment of a multimarker qPCR panel for the molecular characterization of circulating tumor cells in blood samples of metastatic breast cancer patients during the course of palliative treatment

Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer

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