Abstract
BackgroundIt 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.MethodsIn 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.ResultsAmong 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.ConclusionsAlthough 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.
Highlights
Triple-negative breast cancers (TNBCs) are defined as tumors that lack the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
The purpose of this study was to assess Microsatellite instability (MSI) in Japanese female triple-negative breast cancers (TNBCs) to determine the potential use of immune checkpoint inhibitor (ICI) for treatment
We demonstrated that the frequency of MSI-H was 0.9% (2/228) in a relatively large cohort
Summary
Triple-negative breast cancers (TNBCs) are defined as tumors that lack the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The US Food and Drug Administration (FDA) approved anti-PD-1 immune checkpoint inhibitor (ICI), pembrolizumab, for the treatment of adult and pediatric patients with unresectable or metastatic, high-frequency MSI (MSI-H) or dMMR solid tumors in May 2017. These are the first gene level biomarkers for anti-PD-1 ICIs, which were approved in Japan in December 2018. 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. MSI-H breast cancer patients should be picked up using conventional methods and platforms for comprehensive genomic profiling
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