Kelly Gynecologic Oncology Division, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, Minnesota, USA.
Int J Gynecol Cancer. 2021 Aug;31(8):1165-1174. doi: 10.1136/ijgc-2021-002753. Epub 2021 Jul 1.
The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including mutation, mutation/amplification, amplification, amplification, mutation/deletion, mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast-ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.
子宫内膜癌的发病率和死亡率在全球范围内持续上升，而大多数其他癌症的发病率要么已经趋于平稳，要么已经大幅下降。子宫浆液性癌每年在所有子宫内膜恶性肿瘤中所占比例很小，但这种组织学却导致了近 40%的与子宫内膜癌相关的死亡。这些死亡不成比例地影响黑人妇女，她们在诊断时患有晚期疾病的比例更高。分子遗传学分析揭示了主要的改变，包括 突变、 突变/扩增、 扩增、 扩增、 突变/缺失、 突变和涉及同源重组基因的体细胞突变。子宫浆液性癌的临床危险因素包括年龄增长、乳腺癌病史、他莫昔芬使用和遗传性乳腺癌-卵巢癌综合征。手术仍然是治疗的基石。我们对子宫浆液性癌分子驱动因素的理解的最新进展导致了靶向治疗的发展，有望为患者带来更好的结果。子宫浆液性癌中 HER2 的过表达或扩增预示着预后不良；然而，这一可操作的靶点导致了几种抗 HER2 治疗药物的应用，包括曲妥珠单抗，当与常规化疗联合使用时，与晚期和复发性 HER2 阳性疾病女性的生存改善相关。帕博利珠单抗和仑伐替尼的联合也是治疗子宫浆液性癌的一种有前途的靶向治疗策略，最近的一项 II 期研究表明，在复发性疾病的女性中，有 50%的反应率。目前正在进行几项检查其他靶向药物的试验。尽管多年来进展停滞不前，但针对这种罕见且具有生物学侵袭性的子宫内膜癌亚型，出现了有意义的、量身定制的治疗选择。
