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Genetic polymorphisms and correlation with treatment induced cardiotoxicity and prognosis in breast cancer patients.

BACKGROUND
Cardiac toxicity is a serious complication of HER2-directed therapies and anthracyclines. HER2 codon 655 and SLC28A3 gene polymorphisms have been reported to be associated with cardiac toxicity from anti-HER2 and anthracycline therapy, respectively. Association of the polymorphism at HER2 codon 655 with prognosis has also been reported.


METHODS
Whole blood samples from patients treated on a randomized adjuvant breast cancer trial (BCIRG-006) that compared anthracycline-based chemotherapy to trastuzumab plus either anthracycline or non-anthracycline chemotherapy were tested for genetic polymorphisms in HER2 codon 655 and SLC28A3 Genotypes were correlated with cardiac function and disease-free survival (DFS) outcomes.


RESULTS
Of 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 genotype. Additionally, 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 genotype. Follow up time was 10 years. No correlation between DFS, cardiac event rate or mean left ventricular ejection fraction (LVEF) and rs1136201 genotype was seen in the trastuzumab treated or non-trastuzumab treated patients. Moreover, mean LVEF and cardiac event rates were similar in all rs7853758 genotype groups treated with anthracycline-based therapy.


CONCLUSIONS
In the largest study to date to evaluate whether two polymorphisms are associated with DFS and/or cardiac toxicity in HER2 positive breast cancer treated with trastuzumab and/or anthracyclines, we observed no correlation.