Residual Invasive Disease After Neoadjuvant Therapy in Triple-Negative Breast Cancer: Risk Stratification and Postoperative Radiotherapy-Pembrolizumab Integration.
- 1First Clinical Medical College, Inner Mongolia Medical University, Hohhot, Inner Mongolia, People's Republic of China.
- 2Department of Radiation Oncology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People's Republic of China.
Abstract
Residual invasive disease (RD) after neoadjuvant systemic therapy identifies patients with triple-negative breast cancer (TNBC) at increased but heterogeneous recurrence risk. Continued perioperative pembrolizumab may overlap with postoperative radiotherapy (RT), raising unresolved questions about treatment timing and long-term net clinical benefit. This narrative review examines the pathologic definition and distribution of RD, prognostic stratification, mechanistic evidence, and clinical studies of postoperative RT-pembrolizumab integration. Breast-only, nodal-only, and combined breast and nodal RD should be distinguished alongside residual burden. Residual cancer burden, nodal status, tumor-infiltrating lymphocytes, and circulating tumor DNA may inform prognosis or research stratification, but none is validated to predict benefit from a specific RT-pembrolizumab schedule. Longitudinal molecular monitoring and cell-free DNA fragmentomics remain investigational for postoperative treatment selection. DNA repair, hypoxia, metabolic adaptation, tumor-cell plasticity, and immune suppression provide plausible mechanisms of resistance. However, features measured in surgically removed RD cannot be assumed to persist in occult postoperative disease, and much of the supporting evidence is preclinical or derived from other treatment settings. RT may stimulate antitumor immunity while also injuring immune cells. Small nonrandomized postoperative studies support short-term feasibility of concurrent treatment, but do not establish comparative efficacy or long-term safety. Severe adverse events and treatment interruptions have occurred, and late cardiopulmonary injury, fibrosis, and reconstruction outcomes remain insufficiently characterized. Management should preserve timely, guideline-concordant RT and base pembrolizumab continuation or interruption on clinical recovery and toxicity. Prospective comparisons with clearly defined schedules, prespecified RD subgroups, biomarker analyses, and adequate follow-up are needed to establish long-term net clinical benefit.
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BibTeX
@article{jia2026residual,
title = {{Residual Invasive Disease After Neoadjuvant Therapy in Triple-Negative Breast Cancer: Risk Stratification and Postoperative Radiotherapy-Pembrolizumab Integration.}},
author = {Xinyu Jia and Eerdemutu and Yuan Ren and Shiduo Yang and Chang Yang and Qiaochu Ding and Yu Lin},
journal = {Cancer management and research},
year = {2026},
month = oct,
doi = {10.2147/cmar.s653901},
url = {https://europepmc.org/article/MED/42974087},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Residual Invasive Disease After Neoadjuvant Therapy in Triple-Negative Breast Cancer: Risk Stratification and Postoperative Radiotherapy-Pembrolizumab Integration.
AU - Xinyu Jia
AU - Eerdemutu
AU - Yuan Ren
AU - Shiduo Yang
AU - Chang Yang
AU - Qiaochu Ding
AU - Yu Lin
PY - 2026
DA - 2026/10/29
JO - Cancer management and research
DO - 10.2147/cmar.s653901
UR - https://europepmc.org/article/MED/42974087
AB - Residual invasive disease (RD) after neoadjuvant systemic therapy identifies patients with triple-negative breast cancer (TNBC) at increased but heterogeneous recurrence risk. Continued perioperative pembrolizumab may overlap with postoperative radiotherapy (RT), raising unresolved questions about treatment timing and long-term net clinical benefit. This narrative review examines the pathologic definition and distribution of RD, prognostic stratification, mechanistic evidence, and clinical studies of postoperative RT-pembrolizumab integration. Breast-only, nodal-only, and combined breast and nodal RD should be distinguished alongside residual burden. Residual cancer burden, nodal status, tumor-infiltrating lymphocytes, and circulating tumor DNA may inform prognosis or research stratification, but none is validated to predict benefit from a specific RT-pembrolizumab schedule. Longitudinal molecular monitoring and cell-free DNA fragmentomics remain investigational for postoperative treatment selection. DNA repair, hypoxia, metabolic adaptation, tumor-cell plasticity, and immune suppression provide plausible mechanisms of resistance. However, features measured in surgically removed RD cannot be assumed to persist in occult postoperative disease, and much of the supporting evidence is preclinical or derived from other treatment settings. RT may stimulate antitumor immunity while also injuring immune cells. Small nonrandomized postoperative studies support short-term feasibility of concurrent treatment, but do not establish comparative efficacy or long-term safety. Severe adverse events and treatment interruptions have occurred, and late cardiopulmonary injury, fibrosis, and reconstruction outcomes remain insufficiently characterized. Management should preserve timely, guideline-concordant RT and base pembrolizumab continuation or interruption on clinical recovery and toxicity. Prospective comparisons with clearly defined schedules, prespecified RD subgroups, biomarker analyses, and adequate follow-up are needed to establish long-term net clinical benefit.
SN - 1179-1322
ER -