Key result
UGT2B7-161 T-allele variants are linked to ~89% lower cardiotoxicity risk in HER-2-positive breast cancer.
Why the study?
The predictive value of the UGT2B7-161 single nucleotide polymorphism for cardiotoxicity in Chinese HER-2 positive breast cancer patients undergoing combined pertuzumab and trastuzumab therapy required exploration.
Cohort (n=80)
No
May support genotype-guided cardiotoxicity monitoring in HER2+ breast cancer; leaves open prospective validation before clinical adoption.
Objective: To explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy. Methods: Fifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury. Results: There were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity. Conclusion: UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.
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A 2022 study conducted a cohort in HER-2 positive breast cancer (n=80). UGT2B7-161 CT+TT genotype vs. UGT2B7-161 CC genotype was evaluated on Myocardial toxicity (decreased myocardial work events) (OR 0.107, 95% CI 0.023-0.490, p=<0.001). UGT2B7-161 CT and TT genotypes were associated with a significantly lower risk of cardiotoxicity compared to the CC genotype (OR 0.107, 95% CI 0.023-0.490, P < 0.001) in HER-2 positive breast cancer.
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