Predictive and Prognostic Value of Selected MicroRNAs in Luminal Breast Cancer

Abstract

Breast cancer (BrC) is the most frequent malignancy and the leading cause of cancer death among women worldwide. Approximately 70% of BrC are classified as luminal-like subtype, expressing the estrogen receptor. One of the most common and effective adjuvant therapies for this BrC subtype is endocrine therapy. However, its effectiveness is limited, with relapse occurring in up to 40% of patients. Because microRNAs have been associated with several mechanisms underlying endocrine resistance and sensitivity, they may serve as predictive and/or prognostic biomarkers in this setting. Hence, the main goal of this study was to investigate whether miRNAs deregulated in endocrine-resistant BrC may be clinically relevant as prognostic and predictive biomarkers in patients treated with adjuvant endocrine therapy. A global expression assay allowed for the identification of microRNAs differentially expressed between luminal BrC patients with or without recurrence after endocrine adjuvant therapy. Then, six microRNAs were chosen for validation using quantitative reverse transcription polymerase chain reaction in a larger set of tissue samples. Thus, miR-30c-5p, miR-30b-5p, miR-182-5p, and miR-200b-3p were found to be independent predictors of clinical benefit from endocrine therapy. Moreover, miR-182-5p and miR-200b-3p displayed independent prognostic value for disease recurrence in luminal BrC patients after endocrine therapy. Our results indicate that selected miRNAs’ panels may constitute clinically useful ancillary tools for management of luminal BrC patients. Nevertheless, additional validation, ideally in a multicentric setting, is required to confirm our findings.

miRNA Expression Profiles in Luminal A Breast Cancer—Implications in Biology, Prognosis, and Prediction of Response to Hormonal Treatment

“…Regarding the evaluation of the likelihood of recurrence and resistance to therapeutics such as endocrine resistance [ 83 , 88 , 89 ], the expression of miRNAs should be tested in primary tumor sites, ideally in multicenter studies. Moreover, in vitro evaluation might contribute to the functional characterization of specific miRNAs [ 62 ]. Above all, the role of miRNA expression in liquid biopsies highlights its role as a non-invasive biomarker [ 67 ].…”

“…Also, the analysis of 139 BC tissue samples revealed that downregulation of miR-182-5p and miR-200b-3p represents independent prognostic parameter for disease recurrence in patients with luminal BC after endocrine therapy. Decreased disease-free survival is connected with the downregulation of miR-30 family (miR-30b-5p, miR-30c-5p) [ 62 ]. On the other hand, a global miRNA screen in primary tumors of 6 matched pairs of ER-positive, postmenopausal BC patients treated with tamoxifen (either recurrence-free or developed a recurrence) suggested that higher expression of miR-126 and miR-10a is seen in patients with longer relapse-free survival.…”

Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

“…MiR-138 led cells to proliferation, inhibited apoptosis in vivo, and the tumor suppressor candidate TUSC2 was shown to be a direct target of miR-138. Amorim et al [45] investigated miRNAs expression levels in 139 Luminal BC and identified a panel of four miRNAs (miR-30c-5p, 30b-5p, 182-5p, 200b-3p) as independent predictors of endocrine therapy benefits. MiR-182-5p and 200b-3p provided prognostic information about recurrence following endocrine therapy.…”

Regulation of cell growth and migration by miR-96 and miR-183 in a breast cancer model of epithelial-mesenchymal transition

“…Current research on microRNAs has generally focused on their use as a diagnostic tool [14,15]. In regards to miR-96 and miR-183, a correlative relationship between these microRNAs and patient prognosis has been observed, indicating their potential use as biomarkers [16].…”