UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan
Abstract Background 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. Methods In this retrospective study, we sought to evaluate the a...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-08-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.70096 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850158463649316864 |
|---|---|
| author | Megan H. Wong Veronica C. Jones Wai Yu Linda D. Bosserman Sayeh M. Lavasani Niki Patel Mina S. Sedrak Daphne B. Stewart James R. Waisman Yuan Yuan Joanne E. Mortimer |
| author_facet | Megan H. Wong Veronica C. Jones Wai Yu Linda D. Bosserman Sayeh M. Lavasani Niki Patel Mina S. Sedrak Daphne B. Stewart James R. Waisman Yuan Yuan Joanne E. Mortimer |
| author_sort | Megan H. Wong |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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). Results We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple‐negative breast cancer, five were homozygous for UGT1A1*28 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. Conclusion 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. |
| format | Article |
| id | doaj-art-0465163b93754afbb3f4e1d59911ae8a |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-0465163b93754afbb3f4e1d59911ae8a2025-08-20T02:23:51ZengWileyCancer Medicine2045-76342024-08-011316n/an/a10.1002/cam4.70096UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecanMegan H. Wong0Veronica C. Jones1Wai Yu2Linda D. Bosserman3Sayeh M. Lavasani4Niki Patel5Mina S. Sedrak6Daphne B. Stewart7James R. Waisman8Yuan Yuan9Joanne E. Mortimer10Department of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Breast Surgery City of Hope Comprehensive Cancer Center Duarte California USADepartment of Ambulatory Pharmacy City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USADepartment of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte California USAAbstract Background 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. Methods 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). Results We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple‐negative breast cancer, five were homozygous for UGT1A1*28 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. Conclusion 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.https://doi.org/10.1002/cam4.70096metastatic breast cancerpharmacogeneticssacituzumab govitecanSN‐38 toxicityUGT1A1*28 |
| spellingShingle | Megan H. Wong Veronica C. Jones Wai Yu Linda D. Bosserman Sayeh M. Lavasani Niki Patel Mina S. Sedrak Daphne B. Stewart James R. Waisman Yuan Yuan Joanne E. Mortimer UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan Cancer Medicine metastatic breast cancer pharmacogenetics sacituzumab govitecan SN‐38 toxicity UGT1A1*28 |
| title | UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan |
| title_full | UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan |
| title_fullStr | UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan |
| title_full_unstemmed | UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan |
| title_short | UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan |
| title_sort | ugt1a1 28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan |
| topic | metastatic breast cancer pharmacogenetics sacituzumab govitecan SN‐38 toxicity UGT1A1*28 |
| url | https://doi.org/10.1002/cam4.70096 |
| work_keys_str_mv | AT meganhwong ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT veronicacjones ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT waiyu ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT lindadbosserman ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT sayehmlavasani ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT nikipatel ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT minassedrak ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT daphnebstewart ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT jamesrwaisman ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT yuanyuan ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan AT joanneemortimer ugt1a128polymorphismandtheriskoftoxicityanddiseaseprogressioninpatientswithbreastcancerreceivingsacituzumabgovitecan |