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Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer.

ABSTRACT: BACKGROUND:Circulating microRNAs (miRNAs) have been indicated as predictive biomarkers in breast cancer. We aimed to explore the association of plasma miRNA dynamics with response to neoadjuvant chemotherapy (NCT) and disclose early markers for predicting sensitivity. METHODS:One hundred and nine patients with operable or locally advanced breast cancer, who participated in a prospective clinical trial and received NCT, were analyzed. Blood samples were collected before random assignment, after two cycles of chemotherapy (C2) and before surgery. Based on their clinical response, the patients were defined as chemo-sensitive or insensitive. First, baseline and preoperative samples of selected cases from both groups were screened via TaqMan miRNA array for candidate miRNAs. Afterward all the biospecimens were tested for the candidate miRNAs (miR-222, miR-20a, miR-451, miR-9, miR-34a, miR-155, and miR-145) by quantitative real-time PCR. Finally, logistic regression model was utilized to determine the predictive value of baseline/C2 expression of these miRNAs. RESULTS:Based on the results of microRNA profiling, seven miRNAs were selected for further validation. In the HR+/HER2- cohort (n = 51) dynamics of three miRNAs, including miR-222, miR-20a, and miR-451, were associated with chemo-sensitivity. Importantly, across all the three subtypes we consistently identified chemo-induced decrease in plasma miR-34a in the insensitive patients. Finally, baseline miR-222 overexpression (OR = 6.422, P = 0.049), C2 miR-20a up-regulation (OR = 0.144, P = 0.021) and C2 miR-451 down-regulation (OR = 8.213, P = 0.012) were predictive markers of response to NCT in HR+/HER2- breast cancer. CONCLUSIONS:We described that dynamics of circulating miRNAs might help predict clinical response to NCT in breast cancer.

SUBMITTER: Zhu W

PROVIDER: S-EPMC6144164 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer.

Zhu Wenjie W Liu Mei M Fan Ying Y Ma Fei F Xu Ningzhi N Xu Binghe B

Cancer medicine 20180811 9

<h4>Background</h4>Circulating microRNAs (miRNAs) have been indicated as predictive biomarkers in breast cancer. We aimed to explore the association of plasma miRNA dynamics with response to neoadjuvant chemotherapy (NCT) and disclose early markers for predicting sensitivity.<h4>Methods</h4>One hundred and nine patients with operable or locally advanced breast cancer, who participated in a prospective clinical trial and received NCT, were analyzed. Blood samples were collected before random assi ...[more]

PMID: 30099860

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Project description:PurposemiRNAs have been linked to chemosensitivity of breast cancer cells in vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether (I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and (II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients.MethodsSixty-four patients with newly diagnosed large (≥3 cm) or locally advanced primary breast cancers who underwent neoadjuvant anthracycline/taxane-based chemotherapy were included. Relative expression of 10 miRNAs likely to be associated with chemotherapy response (miR-7,-21,-29a,-29b,-34a,-125b,-155,-200c,-340,-451) was determined by quantitative RT-PCR from pretherapeutic biopsies (n = 64) and residual invasive tumor after chemotherapy (n = 42). Pathologic complete response (pCR) defined by absence of invasive tumor served as reference standard. In addition, miRNA expression was compared with disease-free and overall survival.ResultsNine (14%) of 64 patients achieved pCR. High expression of miR-7 and low expression of miR-340 in pretherapeutic biopsies predicted pCR with a negative predictive value of 96 and 97%, respectively (specificity 54 and 57%). The combined profile of miR-7high/miR-340low demonstrated improved specificity of 86% while maintaining a high negative predictive value (96%) to identify non-responders. Pretherapeutic expression of miR-200c and miR-155 showed prognostic information, and low expression was associated with increased overall survival (115 vs. 90 months, p ≤ 0.03). After chemotherapy, the overall survival of patients with residual invasive tumor was better for those demonstrating low miR-7 or high miR-125b (p = 0.01).ConclusionsIntratumoral expression of miR-7 and miR-340 prior to neoadjuvant chemotherapy could be used to predict pCR and a profile of miR-7low or miR-340high identified patients unlikely to achieve pCR who might benefit from alternative treatment options including earlier surgery. Our study identifies miRNAs as promising predictive biomarkers, which could aid in optimization of breast cancer management and treatment stratification.

Project description:Background and Objective:Systemic inflammation response index (SIRI=N×M/L), based on neutrophil (N), monocyte (M), and lymphocyte (L) counts, is used to predict the survival of patients with malignant tumors and can fully evaluate the balance between host immune and inflammatory condition. The present study is aimed to evaluate the potential prognostic significance of SIRI in patients with breast cancer undergoing neoadjuvant chemotherapy. Subjects and Methods:A total of 262 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of SIRI by receiver operating characteristic curve stratified patients into low SIRI (<0.85×109/L) group and high SIRI (?0.85×109/L) group. The associations between breast cancer and clinicopathological variables by SIRI were determined by chi-square test or Fisher's exact test. Kaplan-Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SIRI. The toxicity of neoadjuvant chemotherapy was evaluated by the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:The results were shown that SIRI had prognostic significance by optimal cutoff value of 0.85×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Compared with patients who had high SIRI, patients with low SIRI had longer DFS and OS (41.27 vs 30.45 months, HR: 1.694, 95% CI: 1.128-2.543, P=0.011; 52.86 vs 45.75 months, HR: 1.288, 95% CI: 0.781-3.124, P=0.002, respectively). The patients with low SIRI had better 3-, 5-, and 10-year rates of DFS and OS than those with high SIRI. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the SIRI had no significance on toxicities of all enrolled patients, excepted diarrhea. In patients without neural invasion, those with low SIRI had better prognosis and lower recurrence rates than those with high SIRI. Conclusion:Pretreatment SIRI with the advantage of repeatable, convenient, and non-invasive is a useful prognostic indicator for breast cancer patients who received neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Dataset Information

Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer.

Publications

Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer.

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