Independent replication of polymorphisms predicting toxicity in breast cancer patients randomized between dose-dense and docetaxel-containing adjuvant chemotherapy

Abstract

Introduction: Although pharmacogenomics has evolved substantially, a predictive test for chemotherapy toxicity is still lacking. We compared the toxicity of adjuvant dose-dense doxorubicin-cyclophosphamide (ddAC) and docetaxel-doxorubicincyclophosphamide (TAC) in a randomized multicenter phase III trial and replicated previously reported associations between genotypes and toxicity. Results: 646 patients (97%) were evaluable for toxicity (grade 2 and higher). Whereas AN was more frequent after ddAC (P < 0.001), TAC treated patients more often had PNP (P < 0.001). We could replicate 2 previously reported associations: TECTA (rs1829; OR 4.18, 95% CI 1.84-9.51, P = 0.001) with PNP, and GSTP1 (rs1138272; OR 2.04, 95% CI 1.13-3.68, P = 0.018) with PNP. Materials and methods: Patients with pT1-3, pN0-3 breast cancer were randomized between six cycles A60C600 every 2 weeks or T75A50C500 every 3 weeks. Associations of 13 previously reported single nucleotide polymorphisms (SNPs) with the most frequent toxicities: anemia (AN), febrile neutropenia (FN) and peripheral neuropathy (PNP) were analyzed using logistic regression models. Conclusions: In this independent replication, we could replicate an association between 2 out of 13 SNPs and chemotherapy toxicities. These results warrant further validation in order to enable tailored treatment for breast cancer patients.