A Correlation Analysis Between Metabolism-related Genes and Treatment Response to S-1 as First-line Chemotherapy for Metastatic Breast Cancer: The SELECT BC-EURECA Study

Tsutomu Takashima, Fumikata Hara, Takayuki Iwamoto, Yukari Uemura, Shozo Ohsumi, Daisuke Yotsumoto, Yasuo Hozumi, Takanori Watanabe, Tsuyoshi Saito, Ken ichi Watanabe, Junji Tsurutani, Tatsuya Toyama, Hiromitsu Akabane, Reiki Nishimura, Naruto Taira, Yasuo Ohashi, Hirofumi Mukai

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The previous randomized phase 3 trial (SELECT BC) showed that S-1 as a first-line chemotherapy for metastatic breast cancer (MBC) is non-inferior to taxane with respect to overall survival. This study aimed to identify the usefulness of metabolism-related genes as predictive biomarkers for the response to S-1 compared with taxane using tumor tissue samples from the previous trial. Patients and Methods: In this SELECT BC-EURECA study, 147 patients with human epidermal growth factor 2 (HER2)-negative MBC who received either S-1 or taxane were evaluated. Formalin-fixed paraffin-embedded specimens were collected, and 14 genes involved in the pyrimidine metabolic pathway, estrogen receptor, progesterone receptor, HER2, Ki67, and beta-tubulin were measured using reverse transcription polymerase chain reaction in microdissected tumor specimens. The expression of each gene was categorized as low, intermediate, and high by tertile values. Results: Interaction tests to identify biomarkers for the response to S-1 compared with taxane, revealed the following as the top 3 biomarkers: RRM1 (P value = 0.24), GGH (P value = 0.25), and MTHFR (P value = 0.28). In the S-1 group, lower GGH and higher MTHFR expression were significantly correlated with better time to treatment failure. In the taxane group, there was no gene that was identified as a significant indicator of treatment failure. Conclusion: This biomarker analysis from SELECT BC did not identify any predictive biomarkers for the response to S-1 compared with taxane. Future studies with larger sample size and information on not only mRNA, but also protein and DNA for broad functional analyses are needed. Our previous randomized phase 3 trial showed that S-1 as a first-line chemotherapy for metastatic breast cancer is noninferior to taxane with respect to overall survival. In this study, we investigated the usefulness of metabolism-related genes as predictive biomarkers of treatment response to S-1 from the previous trial. We found no association between metabolic-related genes and treatment response to S-1.

Original languageEnglish
JournalClinical Breast Cancer
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Biomarker
  • taxane

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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