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.

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.

• Authors: 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
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 21 Issue 5 Pg. 450-457 (10 2021) ISSN: 1938-0666 [Electronic] United States
• PMID: 33685834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• Receptors, Estrogen
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Receptor, ErbB-2

Topics

• Antimetabolites, Antineoplastic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Drug Combinations
• Female
• Health Status
• Humans
• Oxonic Acid (therapeutic use)
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Tegafur (therapeutic use)