Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches.
Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches.
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DOI：
10.3389/fonc.2021.667397
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发表时间：
2021
影响因子：
4.7
通讯作者：
DeMichele A
中科院分区：
文献类型：
--
作者：
Cescon DW;Kalinsky K;Parsons HA;Smith KL;Spears PA;Thomas A;Zhao F;DeMichele A
虽然大多数乳腺癌在可治愈阶段被诊断出来，但大约 20% 的女性在一生中会经历远处复发。目前的治疗方法无法治愈这些转移性复发。在过去的十年中，这些复发背后的生物学机制已被阐明，确定了以循环微转移和休眠疾病形式存在的微小残留病，主要存在于骨髓中。现在有许多技术可用于检测乳腺癌治疗后的微小残留病 (MRD)，但尚不清楚如何最好地靶向和根除这些细胞，以及在明显转移形成之前清除可检测到的疾病是否可以防止最终进展和死亡。由于血液和骨髓中 MRD 的罕见性，检验这一假设的临床试验具有挑战性，因此需要筛查大量幸存者以识别可供研究的幸存者。使用预后分子工具可能能够直接筛查那些最有可能携带 MRD 的患者，但这些预测因素与 MRD 检测之间的关系尚未明确。进一步的挑战包括缺乏具有既定临床实用性的明确 MRD 检测方法、由于了解 MRD 生物学的局限性而难以选择潜在的干预措施，以及检测 MRD 对已完成明确治疗且没有明显转移性疾病证据的患者的情绪影响。本综述为在设计和实施介入性临床试验时应对这些挑战提供了路线图，旨在消除 MRD 并最终预防转移性疾病，以提高该疾病的生存率，特别关注 ER+ 乳腺癌的晚期复发。
While the majority of breast cancers are diagnosed at a curable stage, approximately 20% of women will experience recurrence at a distant site during their lifetime. These metastatic recurrences are incurable with current therapeutic approaches. Over the past decade, the biologic mechanisms underlying these recurrences have been elucidated, establishing the existence of minimal residual disease in the form of circulating micrometastases and dormant disease, primarily in the bone marrow. Numerous technologies are now available to detect minimal residual disease (MRD) after breast cancer treatment, but it is yet unknown how to best target and eradicate these cells, and whether clearance of detectable disease prior to the formation of overt metastases can prevent ultimate progression and death. Clinical trials to test this hypothesis are challenging due to the rare nature of MRD in the blood and bone marrow, resulting in the need to screen a large number of survivors to identify those for study. Use of prognostic molecular tools may be able to direct screening to those patients most likely to harbor MRD, but the relationship between these predictors and MRD detection is as yet undefined. Further challenges include the lack of a definitive assay for MRD with established clinical utility, difficulty in selecting potential interventions due to limitations in understanding the biology of MRD, and the emotional impact of detecting MRD in patients who have completed definitive treatment and have no evidence of overt metastatic disease. This review provides a roadmap for tackling these challenges in the design and implementation of interventional clinical trials aimed at eliminating MRD and ultimately preventing metastatic disease to improve survival from this disease, with a specific focus on late recurrences in ER+ breast cancer.
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DOI：
10.1200/jco.20.02514
发表时间：
2020-12-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Johnston SRD;Harbeck N;Hegg R;Toi M;Martin M;Shao ZM;Zhang QY;Martinez Rodriguez JL;Campone M;Hamilton E;Sohn J;Guarneri V;Okada M;Boyle F;Neven P;Cortés J;Huober J;Wardley A;Tolaney SM;Cicin I;Smith IC;Frenzel M;Headley D;Wei R;San Antonio B;Hulstijn M;Cox J;O'Shaughnessy J;Rastogi P;monarchE Committee Members and Investigators
通讯作者：
monarchE Committee Members and Investigators
影响因子：
28.4
作者：
Garcia-Murillas, Isaac;Chopra, Neha;Turner, Nicholas C.
通讯作者：
Turner, Nicholas C.
影响因子：
45.3
作者：
Henry, N. Lynn;Azzouz, Faouzi;Storniolo, Anna Maria
通讯作者：
Storniolo, Anna Maria
影响因子：
3.4
作者：
Ibrahim, Ezzeldin M.;Al-Hajeili, Marwan R.;Refae, Ahmed A.
通讯作者：
Refae, Ahmed A.
影响因子：
158.5
作者：
Cardoso, F.;van't Veer, L. J.;Piccart, M.
通讯作者：
Piccart, M.