Microsatellite instability in Japanese female patients with triple-negative breast cancer

Kanako Kurata, Makoto Kubo, Masaya Kai, Hitomi Mori, Hitomi Kawaji, Kazuhisa Kaneshiro, Mai Yamada, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Masayuki Okido, Yoshinao Oda, Masafumi Nakamura

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Abstract

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.

Original languageEnglish
Pages (from-to)490-498
Number of pages9
JournalBreast Cancer
Volume27
Issue number3
DOIs
Publication statusPublished - May 1 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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  • Cite this

    Kurata, K., Kubo, M., Kai, M., Mori, H., Kawaji, H., Kaneshiro, K., Yamada, M., Nishimura, R., Osako, T., Arima, N., Okido, M., Oda, Y., & Nakamura, M. (2020). Microsatellite instability in Japanese female patients with triple-negative breast cancer. Breast Cancer, 27(3), 490-498. https://doi.org/10.1007/s12282-019-01043-5