Exploring therapeutic effects of a CDK4/6 inhibitor on suppressing late recurrence in breast cancer
- 1Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine
- 2Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Abstract
Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, was previously examined in a randomized clinical trial for the adjuvant setting, using invasive disease-free survival (IDFS) as the primary endpoint. Analysis of these IDFS data using a piecewise hazard model suggested that the hazard ratio for IDFS remained reduced even after completion of the two-year abemaciclib treatment, possibly yielding a sustained recurrence-suppressive effect beyond the treatment period. Preclinical and clinical observations have implicated cancer stem cells (CSCs) in treatment-resistant recurrence, including late recurrence, in breast cancer. CSCs are believed to enter a dormant state, enabling them to evade therapeutic targeting and later give rise to recurrence. Therefore, recurrence events cannot be suppressed following treatment conclusion without therapeutic efficacy against dormant CSCs, even if recurrence-suppressive effects are observed during the treatment period. In the current study, we aimed to explore the possible mechanisms underlying the long-term suppressive effect of abemaciclib treatment on recurrence using an existing tumor recurrence prediction model with suitable modifications. This model was operated using CSC-related assumptions, specifically that two distinct sources of recurrence were present after primary tumor resection: (i) metastatic cells already in a proliferative state at the time of surgery and (ii) proliferative metastatic cells newly derived from CSCs after surgery. The results of prediction-based investigations, including the current study, have suggested that therapeutic effects targeting CSCs could at least partially account for the sustained suppression of recurrence observed with abemaciclib treatment of breast cancer.
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BibTeX
@article{nakamura2026exploring,
title = {{Exploring therapeutic effects of a CDK4/6 inhibitor on suppressing late recurrence in breast cancer}},
author = {Akira Nakamura and Yukinori Ozaki and Satoshi Morita},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-64176-6},
url = {https://doi.org/10.1038/s41598-026-64176-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exploring therapeutic effects of a CDK4/6 inhibitor on suppressing late recurrence in breast cancer
AU - Akira Nakamura
AU - Yukinori Ozaki
AU - Satoshi Morita
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-64176-6
UR - https://doi.org/10.1038/s41598-026-64176-6
AB - Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, was previously examined in a randomized clinical trial for the adjuvant setting, using invasive disease-free survival (IDFS) as the primary endpoint. Analysis of these IDFS data using a piecewise hazard model suggested that the hazard ratio for IDFS remained reduced even after completion of the two-year abemaciclib treatment, possibly yielding a sustained recurrence-suppressive effect beyond the treatment period. Preclinical and clinical observations have implicated cancer stem cells (CSCs) in treatment-resistant recurrence, including late recurrence, in breast cancer. CSCs are believed to enter a dormant state, enabling them to evade therapeutic targeting and later give rise to recurrence. Therefore, recurrence events cannot be suppressed following treatment conclusion without therapeutic efficacy against dormant CSCs, even if recurrence-suppressive effects are observed during the treatment period. In the current study, we aimed to explore the possible mechanisms underlying the long-term suppressive effect of abemaciclib treatment on recurrence using an existing tumor recurrence prediction model with suitable modifications. This model was operated using CSC-related assumptions, specifically that two distinct sources of recurrence were present after primary tumor resection: (i) metastatic cells already in a proliferative state at the time of surgery and (ii) proliferative metastatic cells newly derived from CSCs after surgery. The results of prediction-based investigations, including the current study, have suggested that therapeutic effects targeting CSCs could at least partially account for the sustained suppression of recurrence observed with abemaciclib treatment of breast cancer.
SN - 2045-2322
ER -