Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

Pestrin, Marta; Bessi, Silvia; Galardi, Francesca; Truglia, M.; Biggeri, Annibale; Biagioni, Chiara; Cappadona, Silvia; Biganzoli, Laura; Giannini, A. James; Leo, Angelo Di

doi:10.1007/s10549-009-0461-7

Cited by 195 publications

(147 citation statements)

References 36 publications

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“…Nevertheless, such discrepancies between the levels of ER and HER2 measured in the primary tumor and metastases and CTCs have been described before at both the mRNA and the protein level (40,45,(48)(49)(50)(51), indicating that the findings with our multigene measuring technique may indeed be relevant, not only for ER and HER2 but also for the other markers included in our panel.…”

Section: Discussionmentioning

confidence: 62%

mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Sieuwerts

Mostert

Vries

et al. 2011

Clinical Cancer Research

208

158

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Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer.Experimental Design: CTCs were isolated with the epithelial cell adhesion molecule-based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors.Results: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels.Conclusions: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs.

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Section: Discussionmentioning

confidence: 62%

mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Sieuwerts

Mostert

Vries

et al. 2011

Clinical Cancer Research

208

158

View full text Add to dashboard Cite

show abstract

“…Currently, therapeutic decisions are mainly based on primary tumor markers. However, several studies have shown a high degree of discordance between the primary tumor and metastatic sites or CTCs with respect to hormone receptor and HER2 expression (40)(41)(42)(43). Given the estimated short life span of CTCs in the circulation (44), the presence of CTCs in the peripheral blood of breast cancer patients after primary tumor resection suggests that the pool of CTCs is replenished by occult micrometastases.…”

Section: Discussionmentioning

confidence: 99%

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Janni

Rack

Terstappen

et al. 2016

Clinical Cancer Research

330

234

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Purpose: Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTC) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis.Experimental Design: We conducted a pooled analysis of individual data from 3,173 patients with nonmetastatic (stage I-III) breast cancer from five breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the FDA-cleared CellSearch System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months.Results: One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histologic tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histologic tumor grade, and hormone receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival [HR, 1.82; 95% confidence interval (CI), 1.47-2.26], distant disease-free survival (HR, 1.89; 95% CI, 1.49-2.40), breast cancer-specific survival (HR, 2.04; 95% CI, 1.52-2.75), and overall survival (HR, 1.97; 95% CI, 1.51-2.59).

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“…Our study indicates the need for more comprehensive analysis of tissue and ctDNA NGS concordance beyond single genes and hotspot regions to determine utility and potential clinical applications of ctDNA biopsies. Interestingly, studies investigating concordance in biomarker expression between tissue analysis and CTCs, another component of liquid biopsies, have reported a lack of concordance between the two compartments with regards to hormone receptor and HER2 expression (36)(37)(38)(39). These findings clearly demonstrated phenotypic heterogeneity in both primary and metastatic breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Circulating Tumor DNA in Breast Cancer

Chae

Davis

Jain

et al. 2017

Molecular Cancer Therapeutics

119

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While identifying genomic alterations in tumor tissue is the current gold-standard technique for molecular profiling, circulating tumor DNA (ctDNA) represents a noninvasive method of assessing genomic alterations using peripheral blood. The concordance of genomic alterations between two commercially available ctDNA and tissue biopsies was compared in 45 patients with breast cancer using paired next-generation sequencing tissue and ctDNA biopsies. Across all genes, concordance between the two platforms was 91.0% to 94.2%. When only considering genomic alterations in either assay (e.g., excluding wild type/wild type genes), concordance was 10.8% to 15.1% with full plus partial concordance of 13.8% to 19.3%. Concordant mutations were associated with significantly higher variant allele frequency. Over half of mutations detected in either technique were not detected using the other biopsy technique. Including variants of unknown significance, the average number of alterations per patient was significantly higher for tissue (4.56) compared with ctDNA (2.16). When eliminating alterations not detectable in the ctDNA assay, mean number of alterations for tissue and ctDNA was similar (2.67 for tissue, 2.16 for ctDNA). Across five representative genes (TP53, PIK3CA, ERBB2, BRCA1, and BRCA2), sensitivity and specificity were 35.7% and 95.0%, respectively. Concordance when genomic alterations was detected in either tissue or ctDNA was low with each technique detecting a significant amount of nonoverlapping mutations. Potential explanations for the lack of concordance include tumor heterogeneity, different sequencing techniques, spatial and temporal factors, and potential germline DNA contamination. The study indicates that both tissue and blood-based NGS may be necessary to describe the complex biology of breast cancer.

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Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

Cited by 195 publications

References 36 publications

mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Circulating Tumor DNA in Breast Cancer

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