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A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens.

ABSTRACT: The challenge of predicting which patients with breast cancer will develop metastases leads to the overtreatment of patients with benign disease and to the inadequate treatment of aggressive cancers. Here, we report the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast cancer specimens, for the assessment of their metastatic propensity and for the rapid screening of potential antimetastatic therapeutics. On the basis of the key roles of cell motility and proliferation in cancer metastasis, the device accurately predicts the metastatic potential of breast cancer cell lines and of patient-derived xenografts. Compared with unsorted cancer cells, highly motile cells isolated by the device exhibited similar tumourigenic potential but markedly increased metastatic propensity in vivo. RNA sequencing of the highly motile cells revealed an enrichment of motility-related and survival-related genes. The approach might be developed into a companion assay for the prediction of metastasis in patients and for the selection of effective therapeutic regimens.

SUBMITTER: Yankaskas CL

PROVIDER: S-EPMC6563615 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens.

Yankaskas Christopher L CL Thompson Keyata N KN Paul Colin D CD Vitolo Michele I MI Mistriotis Panagiotis P Mahendra Ankit A Bajpai Vivek K VK Shea Daniel J DJ Manto Kristen M KM Chai Andreas C AC Varadarajan Navin N Kontrogianni-Konstantopoulos Aikaterini A Martin Stuart S SS Konstantopoulos Konstantinos K

Nature biomedical engineering 20190506 6

The challenge of predicting which patients with breast cancer will develop metastases leads to the overtreatment of patients with benign disease and to the inadequate treatment of aggressive cancers. Here, we report the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast cancer specimens, for the assessment of their metastatic propensity and for the rapid screening of potential antimetastatic therapeutics. On the basi ...[more]

PMID: 31061459

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Project description:BackgroundMetastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question.ObjectivesTo assess the effects of breast surgery in women with metastatic breast cancer.Search methodsWe conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies.Selection criteriaThe inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy.Data collection and analysisTwo review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies.Main resultsWe included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence).Authors' conclusionsBased on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.

Dataset Information

A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens.

Publications

A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens.

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