Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Department of Breast Surgery, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Cancer Med. 2024 Aug;13(16):e70096. doi: 10.1002/cam4.70096.
Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2-negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity.
In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68).
We found 17 (25%) of our patients to be homozygous for UGT1A128 and 24 (35.3%) were heterozygous. Of seven African American patients with triple-negative breast cancer, five were homozygous for UGT1A128 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression.
This retrospective, real-world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes.
Sacituzumab govitecan（sacituzumab）在转移性和局部复发性 HER2 阴性乳腺癌的治疗中成为一种重要的药物。UGT1A1 多态性也被证明可以预测 sacituzumab 的毒性。
在这项回顾性研究中，我们试图评估接受过 UGT1A1 等位基因（N=68）基因型检测的晚期乳腺癌 sacituzumab 接受者的 UGT1A1 状态、毒性和治疗结果之间的关联。
我们发现 17 名（25%）患者为 UGT1A128 纯合子，24 名（35.3%）为杂合子。在 7 名患有三阴性乳腺癌的非裔美国患者中，有 5 名是 UGT1A128 纯合子，2 名是杂合子。UGT1A1*28 纯合子基因型的患者因不良反应而终止治疗的可能性显著更高。然而，该多态性与因疾病进展而终止治疗无关。
这项回顾性的真实世界分析表明，在接受 sacituzumab 治疗的患者中进行 UGT1A1 检测具有潜在的临床应用价值，但需要进一步的试验来证实基因型与治疗结果之间的关联。
