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Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches
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 underlyi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867255/ https://www.ncbi.nlm.nih.gov/pubmed/35223447 http://dx.doi.org/10.3389/fonc.2021.667397 |
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author | Cescon, David W. Kalinsky, Kevin Parsons, Heather A. Smith, Karen Lisa Spears, Patricia A. Thomas, Alexandra Zhao, Fengmin DeMichele, Angela |
author_facet | Cescon, David W. Kalinsky, Kevin Parsons, Heather A. Smith, Karen Lisa Spears, Patricia A. Thomas, Alexandra Zhao, Fengmin DeMichele, Angela |
author_sort | Cescon, David W. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8867255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88672552022-02-25 Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches Cescon, David W. Kalinsky, Kevin Parsons, Heather A. Smith, Karen Lisa Spears, Patricia A. Thomas, Alexandra Zhao, Fengmin DeMichele, Angela Front Oncol Oncology 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. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8867255/ /pubmed/35223447 http://dx.doi.org/10.3389/fonc.2021.667397 Text en Copyright © 2022 Cescon, Kalinsky, Parsons, Smith, Spears, Thomas, Zhao and DeMichele https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Cescon, David W. Kalinsky, Kevin Parsons, Heather A. Smith, Karen Lisa Spears, Patricia A. Thomas, Alexandra Zhao, Fengmin DeMichele, Angela Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches |
title | Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches |
title_full | Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches |
title_fullStr | Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches |
title_full_unstemmed | Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches |
title_short | Therapeutic Targeting of Minimal Residual Disease to Prevent Late Recurrence in Hormone-Receptor Positive Breast Cancer: Challenges and New Approaches |
title_sort | therapeutic targeting of minimal residual disease to prevent late recurrence in hormone-receptor positive breast cancer: challenges and new approaches |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867255/ https://www.ncbi.nlm.nih.gov/pubmed/35223447 http://dx.doi.org/10.3389/fonc.2021.667397 |
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