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Updated: Jan 6, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant
Yuko Takahashi1, Takayuki Iwamoto2, Yoko Suzuki2
1Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Introduction:
Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy.
Patients And Methods:
We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III.
Results:
Among hormone receptor-positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node-positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II.
Conclusion:
In hormone receptor-positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.
Insights
Patients with residual breast cancer after neoadjuvant chemotherapy have a poor prognosis. This study identified potential therapeutic targets and adjuvant treatments for residual disease, particularly in hormone receptor-positive subtypes.
Area of Science:
- Oncology
- Genomics
- Breast Cancer Research
Background:
- Patients with residual disease after neoadjuvant chemotherapy for breast cancer often face a poor prognosis.
- Identifying therapeutic targets is crucial for improving outcomes in these patients.
Purpose of the Study:
- To explore potential therapeutic targets and adjuvant treatment strategies for patients with residual breast cancer after neoadjuvant chemotherapy.
- To analyze gene expression profiles in relation to residual cancer burden (RCB) classification.
Main Methods:
- Retrieved and analyzed complementary DNA microarray data from 399 HER2-negative primary breast cancer samples.
- Assessed mRNA expression levels of key breast cancer markers and therapeutic target genes based on RCB classification (RCB-0/I, RCB-II, RCB-III).
Main Results:
- Luminal A tumors were more prevalent in RCB-III among hormone receptor-positive samples.
- ESR1 and PGR mRNA expression was higher, and MKI67 was lower in RCB-II/III compared to RCB-0/I.
- VEGF-C expression was significantly higher in RCB-III across both hormone receptor-positive and triple-negative subtypes.
Conclusions:
- Biological features like luminal A are associated with RCB in hormone receptor-positive breast cancer, but not in triple-negative breast cancer.
- Targeted therapies warrant investigation as novel adjuvant strategies in clinical trials for patients with residual disease.
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