A novel three-gene score as a predictive biomarker for pathologically complete response after neoadjuvant chemotherapy in triple-negative breast cancer

Masanori Oshi, Fernando A. Angarita, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Although triple-negative breast cancer (TNBC) typically responds better to neoadjuvant chemotherapy (NAC) compared to the other subtypes, a pathological complete response (pCR) is achieved in less than half of the cases. We established a novel three-gene score using genes based on the E2F target gene set that identified pCR after NAC, which showed robust performance in both training and validation cohorts (total of n = 3862 breast cancer patients). We found that the three-gene score was elevated in TNBC compared to the other subtypes. A high score was associated with Nottingham histological grade 3 in TNBC. Across multiple cohorts, high-score TNBC enriched not only E2F targets but also G2M checkpoint and mitotic spindle, which are all cell proliferation-related gene sets. High-score TNBC was associated with homologous recombination deficiency, high mutation load, and high infiltration of Th1, Th2, and gamma-delta T cells. However, the score did not correlate with drug sensitivity for paclitaxel, 5-fluorouracil, cyclophosphamide, and doxorubicin in TNBC human cell lines. High-score TNBC was significantly associated with a high rate of pCR not only in the training cohort but also in the validation cohorts. High-score TNBC was significantly associated with better survival in patients who received chemotherapy but not in patients who did not receive chemotherapy. The three-gene score is associated with a high mutation rate, immune cell infiltration, and predicts response to NAC in TNBC.

Original languageEnglish (US)
Article number2401
JournalCancers
Volume13
Issue number10
DOIs
StatePublished - May 2 2021

Keywords

  • Neoadjuvant chemotherapy
  • Predictive biomarker
  • Prognosis
  • Three gene
  • Triple-negative breast cancer
  • Tumor immune microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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