当前，液体活检技术方兴未艾，循环肿瘤DNA（ctDNA）监测在乳腺癌精准治疗中展现出巨大潜力。在ESMO BC年会“Educational Session：Adjuvant therapy for ER positive breast cancer”专场上，美国弗雷德·哈钦森癌症研究中心Heather Parsons教授带来了“The role of ctDNA monitoring in ER+eBC:Could it change practice?（ctDNA监测在ER+早期乳腺癌中的作用：能否改变临床实践？）”的讲课，系统阐述了ctDNA在ER+早期乳腺癌中的现状与挑战。她指出，ctDNA检测分子残留病灶（MRD）与远处复发强相关，但ER+乳腺癌ctDNA脱落率低、需连续监测；回顾性研究结果虽令人鼓舞，前瞻性干预证据尚缺乏，目前不推荐临床试验外常规使用。讲课结束后，Heather Parsons教授接受了肿瘤瞭望的现场专访，就ctDNA如何指导个体化治疗降级或升级、以及未来研究方向分享了深刻见解。
编者按：当前，液体活检技术方兴未艾，循环肿瘤DNA（ctDNA）监测在乳腺癌精准治疗中展现出巨大潜力。在ESMO BC年会“Educational Session：Adjuvant therapy for ER positive breast cancer”专场上，美国弗雷德·哈钦森癌症研究中心Heather Parsons教授带来了“The role of ctDNA monitoring in ER+eBC:Could it change practice?（ctDNA监测在ER+早期乳腺癌中的作用：能否改变临床实践？）”的讲课，系统阐述了ctDNA在ER+早期乳腺癌中的现状与挑战。她指出，ctDNA检测分子残留病灶（MRD）与远处复发强相关，但ER+乳腺癌ctDNA脱落率低、需连续监测；回顾性研究结果虽令人鼓舞，前瞻性干预证据尚缺乏，目前不推荐临床试验外常规使用。讲课结束后，Heather Parsons教授接受了肿瘤瞭望的现场专访，就ctDNA如何指导个体化治疗降级或升级、以及未来研究方向分享了深刻见解。
《肿瘤瞭望》：您在此次会议中介绍或重点关注了哪些内容？这些治疗方案对于患者的精准治疗有何重要意义，能否结合您的临床实践进行分享。
Heather Parsons教授：我主要关注循环肿瘤DNA（ctDNA）或游离DNA（cfDNA），这些是血液中发现的、来自癌症的微小DNA片段。我们的正常细胞也会释放这些片段，但我们拥有先进的技术能够检测到癌症DNA的微小片段。
这项技术有多种应用方式，但最具潜力、同时也最难以验证的，是所谓的分子残留病灶（molecular residual disease，MRD），即癌症初始治疗后体内残留的、无法通过影像学检查发现，却可以通过血液检测或其他液体检测手段检出的分子层面的病灶。
这在乳腺癌中具有许多潜在的意义。我们在激素受体阳性（HR+）乳腺癌中观察到，ctDNA的存在与远处复发密切相关，而ctDNA的清除似乎与更好的预后相关。因此，我们的构想是，可以将其作为一种生物标志物，来决定哪些患者应该接受更强的治疗，同时也希望借此确定哪些患者可以减少治疗。
目前面临的挑战是，我们虽然有很多非常令人鼓舞和振奋的回顾性研究，但还尚缺乏足够的前瞻性数据，来指导我们是否以及如何使用ctDNA和MRD来引导治疗决策。
我对这一领域研究非常感兴趣。目前有许多干预性研究正在进行中，我们在本次会议上也看到了TRAK-ER研究相关数据的公布（1O-ctDNA detection rates during surveillance in high-risk HR+/HER2 negative breast cancer from the TRAK-ER study.Speaker：Niamh Cunningham），该研究显示了一些积极的信号，但也暴露出一些挑战：许多患者在影像学扫描时已经出现转移性疾病，并且乳腺癌中ctDNA检测阳性的频率非常非常低，我们在多项研究中都观察到了这一现象。
因此，我认为在开始将该技术应用于早期乳腺癌之前，我们还需要理解并解决许多问题。目前，我们已经将其用于晚期乳腺癌的治疗指导，以检测ESR1、PIK3CA或AKT通路突变等标志物，但在早期乳腺癌的应用上，我们还有很长的路要走。
So I focus on circulating tumor DNA（ctDNA）or cell-free DNA（cfDNA），which is tiny pieces of DNA that are found in the blood that come from the cancer.Our normal cells also release these pieces but we have good technologies that can detect little pieces of the cancer DNA.
And there are lots of ways we can use this technology，but the most exciting one potentially and also the most challenging to prove is what’s called molecular residual disease，which means the molecular disease that is left in the body after initial treatment of cancer that is not able to be detected by imaging studies but can be detected from a blood test or some other liquid test.
And this has a lot of potential implications in breast cancer.What we’ve seen in hormone receptor positive breast cancer is that the presence of ctDNA is very strongly associated with distant recurrence and the clearance of ctDNA does seem to correlate with better outcomes.And so the idea is that we could potentially use this as a biomarker to decide who should get more therapy and also hopefully who should get less therapy.
The challenge right now is that we have a lot of retrospective studies that are very promising and exciting，but we don’t yet have a lot of prospective data that gives us information about whether and how we should use ctDNA and MRD to guide treatment.
And so I’m really excited about this field.There are many interventional studies that are underway and we saw one presented earlier at this meeting by Dr.Turner that showed some promising signals from the TRAK-ER study，but there were also some challenges.Many of the patients already had metastatic disease when they did scans and the frequency of positive tests in breast cancer was very，very low and we’ve seen that across many studies.
So I think there are many pieces that we need to understand and figure out to start using the technology in early breast cancer.We’re already using it to guide therapy to detect markers like ESR1 or PIK3CA or AKT pathway mutations in advanced breast cancer，but we have a long way to go in early breast cancer.
Heather Parsons
弗雷德·哈钦森癌症研究中心（Fred Hutch）临床研究部
弗雷德·哈钦森癌症研究中心乳腺肿瘤学项目部主任
主要研究方向：利用基于基因组的生物标志物和ctDNA来为乳腺癌患者提供治疗。