早期乳腺癌术后复发魔戒克星之王？
众所周知，人类成年以后，正常细胞有丝分裂周期大多逐渐减缓停滞，这主要受到周期蛋白依赖性激酶（CDK）控制。其中，CDK4和CDK6主要控制细胞有丝分裂周期由DNA合成前期（G1）进入DNA合成期（S）。激素受体阳性乳腺癌细胞的基本特征之一就是有丝分裂周期失控，进入疯狂的有丝分裂繁殖恶性循环，这主要由于CDK4和CDK6过度活跃引起，故CDK4和CDK6抑制剂可有效阻断该恶性循环。
哌柏西利、阿贝西利、瑞博西利等CDK4和CDK6抑制剂问世以来，已经显著改善了激素受体阳性晚期乳腺癌患者的生存结局。不过，由于淋巴结阳性激素受体阳性早期乳腺癌术后复发率仍然较高，迫切需要预防此类患者复发的新药，因此术后CDK4和CDK6抑制剂辅助治疗成为合乎逻辑的下一步。
2021年5月28日，美国癌症学会《癌症》在线发表罗彻斯特大学的长篇综述：激素受体阳性乳腺癌术后CDK4和CDK6抑制剂辅助治疗一个君主（Monarch）统御全部？该标题来自英国牛津大学语言学家托尔金教授名著《指环王》至尊魔戒表面用黑暗语写成的腾格瓦文字：One Ring to rule them all，Ring被改为Monarch。
目前，仅三项早期乳腺癌术后CDK抑制剂辅助治疗随机对照研究结果公布：哌柏西利的PALLAS和PENELOPE-B、阿贝西利的MonarchE。
其中，仅MonarchE研究结果表明，CDK抑制剂与单用内分泌治疗相比，具有统计学优势。这些研究既有相似之处，又有不同之处，可以解释不同的结果。
由于MonarchE研究中位随访仅19个月，相比PALLAS研究24个月、PENELOPE-B研究43个月，对于早期乳腺癌患者而言，时间相对较短，继续分析对于确认此类患者术后CDK抑制剂辅助治疗的获益至关重要。
因此，必须确定具有预测作用的生物学标志，有助于此类药物被用于最有可能获益的患者，从而避免不需要此类药物的患者产生不必要的毒性和费用。
相关链接
Cancer. 2021 May 28. Online ahead of print.
Adjuvant cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive breast cancer: One Monarch to rule them all?
Dhakal A, Falkson C, O'Regan RM.
University of Rochester, Rochester, New York.
The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has dramatically improved outcomes for patients with metastatic, hormone receptor (HR)-positive breast cancer. Because of the continued high rate of relapse in patients with node-positive, HR-positive disease, evaluating these agents in the adjuvant setting is the logical next step. Three adjuvant CDK inhibitor trials have been reported to date, with only 1 of them showing a statistical advantage for the CDK inhibitor in comparison with endocrine therapy alone. These trials have key similarities and differences that could explain the disparate results. The one positive trial has a relatively short follow-up, and continued analysis is critical to confirm the benefit of adjuvant CDK inhibition in this setting. It is imperative that predictive biomarkers be determined so that these agents can be used in the patients most likely to benefit and thus the additional toxicity and expense can be avoided in those who do not require these agents.
LAY SUMMARY: There is a critical need for new agents to prevent relapse in patients with hormone receptor-positive breast cancer. Trials to date evaluating cyclin-dependent kinase inhibitors, which decrease how quickly cancer cells multiply, have shown mixed results, with only 1 trial demonstrating that these agents decrease recurrence.
KEYWORDS: biomarker; breast cancer; cyclin-dependent kinase (CDK) inhibitors; endocrine therapy; hormone receptor
PMID: 34047359
DOI: 10.1002/cncr.33650