For a study, researchers sought to understand that Anti-HER2 and anthracycline therapy-related cardiac toxicity had been linked to HER2 codon 655 and SLC28A3 gene polymorphisms, respectively. The polymorphism at HER2 codon 655 had also been linked to poor prognosis. Whole blood samples from patients enrolled in the BCIRG-006 trial, which compared chemotherapy with or without trastuzumab plus either anthracycline or nonanthracycline chemotherapy, were analyzed for genetic polymorphisms in HER2 codon 655 and SLC28A3. Genotypes were linked to cardiac function and disease-free survival (DFS). Of the 3,222 patients enrolled in BCIRG-006, 662 patient samples were successfully genotyped for the rs1136201 allele in HER2 (codon 655): 424 (64%) were AA, 30 (4.5%) were GG, and 208 (31%) were AG. Furthermore, 665 patient samples were successfully genotyped for the rs7853758 allele in the SLC28A3 gene: 19 (3%) were AA, 475 (71%) were GG, and 171 (26%) were AG. The follow-up period was 10 years. In trastuzumab-treated or non–trastuzumab-treated patients, there was no correlation between DFS, cardiac event rate, or mean left ventricular ejection fraction (LVEF) and rs1136201 genotype. Furthermore, all rs7853758 genotype groups treated with anthracycline-based therapy had similar mean LVEF and cardiac event rates. Researchers found no correlation between 2 polymorphisms and DFS and cardiac toxicity in HER2-positive breast cancer patients treated with trastuzumab and anthracyclines in the largest study to date.