TY - JOUR
T1 - A Correlation Analysis Between Metabolism-related Genes and Treatment Response to S-1 as First-line Chemotherapy for Metastatic Breast Cancer
T2 - The SELECT BC-EURECA Study
AU - Takashima, Tsutomu
AU - Hara, Fumikata
AU - Iwamoto, Takayuki
AU - Uemura, Yukari
AU - Ohsumi, Shozo
AU - Yotsumoto, Daisuke
AU - Hozumi, Yasuo
AU - Watanabe, Takanori
AU - Saito, Tsuyoshi
AU - Watanabe, Ken ichi
AU - Tsurutani, Junji
AU - Toyama, Tatsuya
AU - Akabane, Hiromitsu
AU - Nishimura, Reiki
AU - Taira, Naruto
AU - Ohashi, Yasuo
AU - Mukai, Hirofumi
N1 - Funding Information:
All authors contributed to the study conception and design. Material preparation, data collection, and analyses were performed by FH, YU, and HM. The first draft of the manuscript was written by TI, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. We would like to thank the patients, investigators, and institutions involved in this study and also like to thank Editage (www. editage.jp) for English language editing. The research fund was provided by the Comprehensive Support Project for Oncology Research by Taiho Pharmaceutical Co, Ltd under the study contract. Dr Takashima reports personal fees from Taiho Pharmaceutical Co, Ltd; personal fees from Eisai Co, Ltd; personal fees from Chugai Pharmaceutical Co, Ltd; personal fees from Eli Lilly Japan KK; personal fees from Pfizer Japan Inc; personal fees from Novartis Pharma KK; personal fees from Kyowa Hakko Kirin Co, Ltd; and personal fees from Daiichi-Sankyo KK outside the submitted work. Dr Hara reports personal fees from Taiho during the conduct of the study, personal fees from Chugai, personal fees from Pfizer, personal fees from Eli Lilly, personal fees from Kyowa Kirin, and personal fees from Eisai outside the submitted work. Dr Uemura reports personal fees and nonfinancial support from Comprehensive Support Project for Oncology Research in Breast Cancer during the conduct of the study. Dr Hozumi reports personal fees from Chugai, personal fees from Astra Zeneca, personal fees from Pfizer, personal fees from Taiho, and personal fees from Eli Lilly outside the submitted work. Dr Tsurutani reports nonfinancial support from Articulate Science LLC during the conduct of the study, grants and personal fees from Daiichi Sankyo, grants and personal fees from Kyowa Hakko Kirin, personal fees from Taiho, grants and personal fees from Chugai, personal fees from Novartis, grants and personal fees from Eli Lilly, grants and personal fees from Pfizer, personal fees from Nihonkayaku, personal fees from Aasahikasei, grants from JSCO, and grants and personal fees from Eisai outside the submitted work. Dr Toyama reports grants and personal fees from Chugai, grants and personal fees from Daiichi Sankyo, grants and personal fees from Lilly, personal fees from AstraZeneca, grants and personal fees from Novartis, grants and personal fees from Pfizer, grants and personal fees from Taiho, grants and personal fees from Takeda, grants and personal fees from Nippon Kayaku, and grants and personal fees from Kyowa Kirin outside the submitted work. Dr Ohashi reports personal fees from Statcom, personal fees from Daiichi-Sankyo, personal fees from Chugai, personal fees from Shionogi, personal fees from Taiho, personal fees from Sanofi, grants from Medical Member System, and personal fees from EP-Crsu outside the submitted work. Dr Mukai received honoraria from AstraZeneca, Eisai, Pfizer, Takeda, Daiichi Sankyo, and Taiho, and research grants from the Japanese government, Daiichi Sankyo, Eisai, Nippon Kayaku, and Pfizer outside the submitted work. Drs Iwamoto, Osumi, Yotsumoto, T. Watanabe, Saito, K. Watanabe, Akabane, Nishimura, and Taira have nothing to disclose.
Publisher Copyright:
© 2021
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Biomarker
KW - taxane
UR - http://www.scopus.com/inward/record.url?scp=85102113793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102113793&partnerID=8YFLogxK
U2 - 10.1016/j.clbc.2021.01.018
DO - 10.1016/j.clbc.2021.01.018
M3 - Article
C2 - 33685834
AN - SCOPUS:85102113793
VL - 21
SP - 450
EP - 457
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
SN - 1526-8209
IS - 5
ER -
