Amorim Maria, Lobo João, Fontes-Sousa Mário, Estevão-Pereira Helena, Salta Sofia, Lopes Paula, Coimbra Nuno, Antunes Luís, Palma de Sousa Susana, Henrique Rui, Jerónimo Carmen
Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
Master in Oncology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), Porto, Portugal.
Front Genet. 2019 Sep 11;10:815. doi: 10.3389/fgene.2019.00815. eCollection 2019.
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, , , , and were found to be independent predictors of clinical benefit from endocrine therapy. Moreover, and 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.
乳腺癌（BrC）是全球女性中最常见的恶性肿瘤，也是癌症死亡的主要原因。大约70%的BrC被归类为管腔样亚型，表达雌激素受体。对于这种BrC亚型，最常见且有效的辅助治疗方法之一是内分泌治疗。然而，其有效性有限，高达40%的患者会复发。由于微小RNA（microRNA）与内分泌抵抗和敏感性的多种机制有关，它们可能在这种情况下作为预测和/或预后生物标志物。因此，本研究的主要目的是调查在内分泌抵抗性BrC中失调的microRNA是否可作为接受辅助内分泌治疗患者的预后和预测生物标志物具有临床相关性。一项全局表达分析能够识别内分泌辅助治疗后有或无复发的管腔型BrC患者之间差异表达的microRNA。然后，选择了六种microRNA在更大一组组织样本中使用定量逆转录聚合酶链反应进行验证。因此，发现[具体名称1]、[具体名称2]、[具体名称3]和[具体名称4]是内分泌治疗临床获益的独立预测因子。此外，[具体名称5]和[具体名称6]对内分泌治疗后管腔型BrC患者的疾病复发显示出独立的预后价值。我们的结果表明，选定的microRNA组合可能构成用于管腔型BrC患者管理的临床有用辅助工具。然而，需要额外的验证，理想情况下是在多中心环境中，以证实我们的发现。
