The predominant forms of breast cancer (BC) are hormone receptor-positive (HR+) tumors characterized by the expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). Patients with HR+ tumors can benefit from endocrine therapy (ET). Three types of ET are approved for the treatment of HR+ BCs and include selective ER modulators, aromatase inhibitors, and selective ER downregulators. ET is the mainstay of adjuvant treatment in the early setting and the backbone of the first-line treatment in an advanced setting; however, the emergence of acquired resistance can lead to cancer recurrence or progression. The mechanisms of ET resistance are often related to the occurrence of mutations in theESR1gene, which encodes the ER-alpha protein. AsESR1mutations are hardly detectable at diagnosis but are present in 30% to 40% of advanced BC (ABC) after treatment, the timeline of testing is crucial. To manage this resistance,ESR1testing has recently been recommended; in ER+ HER2− ABC and circulating cell-free DNA, so-called liquid biopsy appears to be the most convenient way to detect the emergence ofESR1mutations. Technically, several options exist, including Next Generation Sequencing and ultra-sensitive PCR-based techniques. In this context, personalization of ET through the surveillance ofESR1mutations in the plasma of HR+ BC patients throughout the disease course represents an innovative way to improve the standard of care.
乳腺癌的主要类型为激素受体阳性肿瘤，其特征是表达雌激素受体和/或孕激素受体。激素受体阳性肿瘤患者可从内分泌治疗中获益。目前获批用于治疗激素受体阳性乳腺癌的内分泌治疗药物包括三类：选择性雌激素受体调节剂、芳香化酶抑制剂以及选择性雌激素受体下调剂。内分泌治疗是早期乳腺癌辅助治疗的基石，也是晚期一线治疗的核心方案；然而，获得性耐药的出现可能导致癌症复发或进展。内分泌治疗耐药机制常与编码ER-α蛋白的ESR1基因突变相关。由于ESR1突变在初诊时难以检出，但在治疗后晚期乳腺癌患者中检出率可达30%-40%，因此检测时机的选择至关重要。为应对此类耐药，近期建议开展ESR1检测；在ER阳性HER2阴性晚期乳腺癌患者中，通过循环游离DNA（即液体活检）检测ESR1突变成为最便捷的监测手段。技术上存在多种检测方案，包括新一代测序技术和超灵敏PCR技术。在此背景下，通过全程监测激素受体阳性乳腺癌患者血浆中的ESR1突变来实现个体化内分泌治疗，成为提升标准治疗水平的新途径。
肿瘤(癌症)患者之家