March 10, 2020
National Cancer Center Japan
Keio University School of Medicine
A research group—including Yasuhiro Fujiwara, Deputy Director (at the time) of the National Cancer Center Hospital Japan (President: Hitoshi Nakagama, Chuo-ku, Tokyo) [current President and Chief Executive of the Pharmaceuticals and Medical Devices Agency (PMDA)]; Kenji Tamura, Chief of the Department of Breast and Medical Oncology; Yusuke Tanigawara, Professor at the Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School of Medicine; Tomoyo Imamura, Lecturer (at the time) at the same department [current Associate Professor at the Showa University Advanced Cancer Translational Research Institute]; and Taisei Mushiroda, Team Leader of the Laboratory for Pharmacogenomics at RIKEN—in collaboration with 54 institutions nationwide, conducted the world's first prospective randomized controlled trial on the efficacy of genotype-guided personalized treatment in breast cancer tamoxifen therapy. The results showed that for patients with a poor metabolizer genotype of CYP2D6, the enzyme that activates tamoxifen in the body, increasing the dose of tamoxifen did not improve treatment efficacy, leading to the conclusion that genotype-guided dose personalization is unnecessary.
There are ethnic differences in the prevalence of CYP2D6 poor metabolizer genotypes, with approximately 70% of Japanese people having them. Although numerous retrospective studies have shown conflicting results—some suggesting the current tamoxifen dose is sufficient for poor metabolizers, others that it is insufficient—no definitive conclusion had been reached. The research team was able to investigate this issue, which has a significant impact on the Japanese population, through a prospective study that provides a higher level of evidence, and disseminate the findings globally.
The results of this research were published in the *Journal of Clinical Oncology*, the official journal of the American Society of Clinical Oncology, on February 20, and were also featured in the journal's "Editorials" section as a higher level of evidence from a prospective clinical trial.
Please see below for the full press release.