Reinhardt Florian, Franken André, Fehm Tanja, Neubauer Hans
Department of Obstetrics and Gynecology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
Tumour Biol. 2017 Nov;39(11):1010428317731511. doi: 10.1177/1010428317731511.
The majority of breast cancers are hormone receptor positive due to the expression of the estrogen and/or progesterone receptors. Endocrine therapy is a major treatment option for all disease stages of hormone receptor-positive breast cancer and improves overall survival. However, endocrine therapy is limited by de novo and acquired resistance. Several factors have been proposed for endocrine therapy failures, which include molecular alterations in the estrogen receptor pathway, altered expression of cell-cycle regulators, autophagy, and epithelial-to-mesenchymal transition as a consequence of tumor progression and selection pressure. It is essential to reveal and monitor intra- and intertumoral alterations in breast cancer to allow optimal therapy outcome. Endocrine therapy navigation by molecular profiling of tissue biopsies is the current gold standard but limited in many reasons. "Liquid biopsies" such as circulating-tumor cells and circulating-tumor DNA offer hope to fill that gap in allowing non-invasive serial assessment of biomarkers predicting success of endocrine therapy regimen. In this context, this review will provide an overview on inter- and intratumoral heterogeneity of endocrine resistance mechanisms and discuss the potential role of "liquid biopsies" as navigators to personalize treatment methods and prevent endocrine treatment resistance in breast cancer.
大多数乳腺癌因雌激素和/或孕激素受体的表达而呈激素受体阳性。内分泌治疗是激素受体阳性乳腺癌所有疾病阶段的主要治疗选择，可提高总生存率。然而，内分泌治疗受到原发性和获得性耐药的限制。已提出多种导致内分泌治疗失败的因素，包括雌激素受体途径的分子改变、细胞周期调节因子表达的改变、自噬以及肿瘤进展和选择压力导致上皮-间质转化。揭示和监测乳腺癌肿瘤内和肿瘤间的改变对于实现最佳治疗效果至关重要。通过组织活检的分子谱分析进行内分泌治疗指导是目前的金标准，但因多种原因存在局限性。“液体活检”，如循环肿瘤细胞和循环肿瘤DNA，有望填补这一空白，实现对预测内分泌治疗方案成功的生物标志物进行无创连续评估。在此背景下，本综述将概述内分泌耐药机制的肿瘤间和肿瘤内异质性，并讨论“液体活检”作为指导个性化治疗方法和预防乳腺癌内分泌治疗耐药的潜在作用。
