Abstract
Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer.Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR.Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells.Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression.
Highlights
In breast cancer the hormone receptor status is one of the most important predictive factor [1]
We chose 130 patients with invasive breast cancer from the SUCCESS study based on their receptor status, to assemble a collective that showed a well-balanced distribution of established risk factors including hormone receptor status, lymph node status, tumor stages, and grading
The levels of miR-146a were measured in the plasma of Indian breast cancer patients and were significantly higher than in healthy women, indicating the diagnostic potential of this miR in breast cancer [26]
Summary
In breast cancer the hormone receptor status is one of the most important predictive factor [1]. Since patients with positive hormone receptor status are eligible for endocrine adjuvant and palliative therapy, assessment of estrogen (ER) and progesterone (PR) receptor is routinely carried out. ER-positive tumors are classified as (highly hormone responsive) luminal A or (high proliferative and less hormone responsive) luminal B tumors. Targeted therapies that inhibit ER or ER-activated pathways include the selective ER modulator tamoxifen and the aromatase inhibitor arimidex. Anti-HER2 (human epidermal growth factor receptor 2) therapies include the administration of trastuzumab and lapatinib. In spite of receptor positivity, many tumors can develop resistance to therapy, and the expression pattern of ER, PR and HER2 may change over time as tumors progress and metastasize [2]
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