Clinical utility of genetic signatures in selecting adjuvant treatment: Risk stratification for early vs. late recurrences
Clinical utility of genetic signatures in selecting adjuvant treatment: Risk stratification for early vs. late recurrences
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DOI：
10.1016/j.breast.2015.07.002
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发表时间：
2015-11-01
期刊：
影响因子：
3.9
通讯作者：
Hayes, Daniel F.
中科院分区：
文献类型：
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作者：
Hayes, Daniel F.
在激素受体(HR)阳性的早期乳腺癌患者中，辅助性内分泌治疗(ET)可将远处复发和死亡率降低近一半。虽然HR阳性患者在前5-7年的复发风险低于HR阴性患者，但HR阳性患者在随后的几年中每年的复发率在0.5%至2%之间。延长的辅助剂ET进一步减少了在这一后期的随访中的复发。ET与绝经后副作用(潮热、性功能障碍、情绪变化和体重增加)有关，偶尔的主要毒性(他莫昔芬引起的血栓形成和子宫内膜癌；骨矿物质丢失，以及可能的心脏病伴AIS)在整个治疗过程中持续存在。对既往HR阳性乳腺癌患者在接受ET治疗5年后复发风险的准确和可靠的估计将使适当的延长ET决定成为可能。长期复发的风险与淋巴结状况和肿瘤大小有关，但这些都是相对粗略的。几个小组已经调查了多参数肿瘤生物标记物测试是否可以确定那些复发风险很低的患者，以至于延长ET是不合理的。这些检测包括IHC4、21基因的“OncotypeDX”、12基因的“EndoPredict”、PAM50和2基因的“乳腺癌指数(BCI)”检测。所有这些测试的临床有效性已经确定，每个测试至少有一篇论文，表明在最初的五年辅助内分泌治疗后的5-10年内，远处复发的风险存在统计学上的显著差异。然而，风险很高，尽管每一项研究都代表了一项“前瞻性回顾”研究，但它们需要在后续数据集中得到进一步验证，才能被认为具有“临床实用性”，并被用来阻止潜在的挽救生命的治疗。也许更重要的是，临床乳腺癌社区，特别是患者，需要确定需要将晚期复发的风险降低到多低，才能放弃扩展辅助剂ET的毒副作用。(C)2015爱思唯尔有限公司。保留所有权利。
Adjuvant endocrine therapy (ET) reduces the odds of distant recurrence and mortality by nearly one-half in women with hormone receptor (HR) positive early stage breast cancer. While the risk of recurrence is lower for HR positive than negative patients during the first 5-7 years, HR positive patients suffer ongoing recurrences between 0.5 and 2% year over subsequent years. Extended adjuvant ET further reduces recurrence during this late phase of follow-up. ET is associated with post-menopausal side effects (hot flashes, sexual dysfunction, mood changes, and weight gain), and occasional major toxicities (thrombosis and endometrial cancer with tamoxifen; bone mineral loss and possibly heart disease with AIs) persist throughout therapy. Accurate and reliable estimates of the risk of recurrence after five years of ET for women with prior HR positive breast cancer would permit appropriate extended ET decisions. The risk of long-term relapse is related to lymph node status and size of tumor, but these are relatively crude. Several groups have investigated whether multi-parameter tumor biomarker tests might identify those patients whose risk of recurrence is so low that extended ET is not justified. These assays include IHC4, the 21-gene "OncotypeDX", the 12-gene "Endopredict," the PAM50, and the 2-gene "Breast Cancer Index (BCI)" assays. The clinical validity of all these tests for this use context have been established, with at least one paper for each that shows a statistically significant difference in risk of distant recurrence during the 5-10 years after the initial five years of adjuvant endocrine therapy. However, the stakes are high, and although each of these represents a "prospective retrospective" study, they require further validation in subsequent datasets before they should be considered to have "clinical utility" and are used to withhold potentially life-saving treatment. Perhaps more importantly, the clinical breast cancer community, and especially the patient, need to determine how low the risk of late recurrence needs to be to forego the toxicities and side effects of extended adjuvant ET. (C) 2015 Elsevier Ltd. All rights reserved.