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Published on: February 20, 2017
Microsatellite instability in Japanese female patients with triple-negative breast cancer
Kanako Kurata1, Makoto Kubo2, Masaya Kai1
1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Background:
It is important to identify biomarkers for triple-negative breast cancers (TNBCs). Recently, pembrolizumab, an immune checkpoint inhibitor (ICI) for programmed cell death 1 (PD-1), was approved as a treatment strategy for unresectable or metastatic tumor with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency, such as malignant melanoma, non-small cell lung cancer, renal cell cancer and urothelial cancer. In addition, results from clinical trials suggested that ICI was a promising treatment for TNBCs with accumulated mutations. However, the frequency of MSI in Japanese TNBCs still remains unclear. We aimed to analyze the presence of MSI-H in TNBCs as a biomarker for ICI therapy.
Methods:
In this study, we retrospectively evaluated the MSI of 228 TNBCs using an innovative method, MSI Analysis System Version 1.2 (Promega), consisting of 5 microsatellite markers: BAT-26, NR-21, BAT-25, MONO-27 and NR-24 without a normal tissue control.
Results:
Among 228 tumors, 222 (97.4%) were microsatellite stable, 4 (1.7%) low-frequency MSI and 2 (0.9%) MSI-H, respectively. Two MSI-H tumors were potentially aggressive pathologically as indicated by nuclear grade 3 and high Ki-67 (> 30%), and were classified as basal-like and non-BRCA-like, but were not consistent regarding tumor-infiltrating lymphocytes, CD8 and PD-L1 expression.
Conclusions:
Although we found that MSI-H was uncommon (0.9%) in TNBCs, potential targets for ICIs exist in TNBCs. Therefore, MSI-H breast cancer patients should be picked up using not only conventional methods but also platforms for comprehensive genomic profiling.
Insights
High-frequency microsatellite instability (MSI-H) is rare in Japanese triple-negative breast cancer (TNBC). However, MSI-H status may indicate potential targets for immune checkpoint inhibitor (ICI) therapy in TNBC patients.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating biomarker identification.
- Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) show promise for cancers with high-frequency microsatellite instability (MSI-H).
- The prevalence of MSI-H in Japanese TNBC remains undetermined, impacting ICI therapy selection.
Purpose of the Study:
- To determine the frequency of MSI-H in Japanese TNBC.
- To evaluate MSI-H as a potential biomarker for ICI therapy in TNBC.
Main Methods:
- Retrospective analysis of 228 TNBC cases.
- Utilized the MSI Analysis System Version 1.2 (Promega) with five microsatellite markers.
- Assessed microsatellite instability (MSI) status without normal tissue controls.
Main Results:
- Microsatellite stable (MSS) tumors: 97.4% (222/228).
- Low-frequency MSI (MSI-L) tumors: 1.7% (4/228).
- High-frequency MSI (MSI-H) tumors: 0.9% (2/228), exhibiting aggressive pathological features.
Conclusions:
- MSI-H is uncommon in Japanese TNBC (0.9%).
- Despite rarity, MSI-H TNBC may represent targets for ICI therapy.
- Comprehensive genomic profiling alongside conventional methods is recommended for identifying MSI-H TNBC patients for ICI treatment.
