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印度尼西亚雌激素受体阳性乳腺癌女性他莫昔芬治疗优化的基因分型

Genotyping for Optimization of Tamoxifen Therapy in Indonesian Women with ER+ Breast Cancer.

作者信息

Maggadani Baitha Palanggatan, Junusmin Kathleen Irena, Aldila Fatma, Audrienna Jessica, Rabbani Bijak, Maulana Yusuf, Tanu Sabrina Gabriel, Gabriella Gabriella, Amelia Margareta, Agatha Faustina Audrey, Wijaya Marco, Sormin Stevany Tiurma, Mahendra Caroline, Sani Levana Laksmicitra, Irwanto Astrid, Chan Alexandre, Harmita Harmita, Harahap Yahdiana, Haryono Samuel Johny

机构信息

Faculty of Pharmacy, University of Indonesia, Jakarta 16424, Indonesia.

Nalagenetics Pte Ltd., Bukit Merah, Singapore 169204, Singapore.

出版信息

J Pers Med. 2025 Feb 28;15(3):93. doi: 10.3390/jpm15030093.

Abstract

Certain genotypes are linked to a lower efficacy of tamoxifen therapy. This study aimed to observe polymorphisms and examine the impact of genotyping among tamoxifen-treated breast cancer patients in Indonesia. 150 breast cancer participants were recruited. Buccal swab samples were collected; gDNA was extracted and genotyped using the qPCR method. Blood samples were collected, and measurement of tamoxifen metabolite levels was performed using UPLC-MS/MS. 43.3% (n = 65) of participants were IMs. *10 was the most common haplotype (n = 89, 29.7%), followed by *36 (n = 73, 29.7%), making *10/*36 the most common diplotype (n = 34, 22.7%) in this study. The difference in endoxifen levels between the NM and IM-PM groups at baseline was statistically significant ( ≤ 0.001). A dose increase in tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline ( > 0.05) without exposing IMs to serious side effects. No statistically significant differences were observed between the 20mg group and the 40 mg group on the adjusted OS ( > 0.05) and the adjusted PFS ( > 0.05). Our study observed a considerably high proportion of IMs. The dose adjustment of tamoxifen was proven to significantly and safely improve the level of endoxifen and survival.

摘要

某些基因型与他莫昔芬治疗效果较低有关。本研究旨在观察印度尼西亚接受他莫昔芬治疗的乳腺癌患者的基因多态性并检测基因分型的影响。招募了150名乳腺癌参与者。采集颊拭子样本;提取基因组DNA并使用qPCR方法进行基因分型。采集血样,并使用超高效液相色谱-串联质谱法测定他莫昔芬代谢物水平。43.3%(n = 65)的参与者为中间代谢型。10是最常见的单倍型(n = 89,29.7%),其次是36(n = 73,29.7%),使得*10/*36成为本研究中最常见的双倍型(n = 34,22.7%)。基线时,正常代谢型和中间代谢型-慢代谢型组之间的4-羟基他莫昔芬水平差异具有统计学意义(≤0.001)。他莫昔芬剂量增加至每日40 mg成功将中间代谢型患者的4-羟基他莫昔芬水平提高到与基线时正常代谢型患者相似的水平(>0.05),且未使中间代谢型患者出现严重副作用。在调整后的总生存期(>0.05)和调整后的无进展生存期(>0.05)方面,20mg组和40mg组之间未观察到统计学显著差异。我们的研究观察到相当高比例的中间代谢型。他莫昔芬的剂量调整被证明能显著且安全地提高4-羟基他莫昔芬水平和生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b9/11943653/c54865fd2b82/jpm-15-00093-g001.jpg

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