The impact of EGFR gene polymorphisms on the response and toxicity derived from neoadjuvant chemotherapy for breast cancer.

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy is usually used for treating locally advanced breast cancer. However, not all patients achieve pathologic complete response (pCR). In this study, we selected two epidermal growth factor receptor (EGFR) single nucleotide polymorphism (SNP) sites, rs1468727 and rs845552, to investigate the association between the genotypes and the response and toxicity derived from neoadjuvant chemotherapy for breast cancer. METHODS: All participants took part in clinical trial SHPD001 and SHPD002. For univariate analyses, the association between SNP and pCR or toxicity was analyzed by Chi-square or Fisher's exact test. For multivariate analyses, logistic regression was used instead. RESULTS: In all, one hundred and eighteen patients were enrolled. We found that the frequency of AA genotype in rs845552 was higher than that of other genotypes in HER2-positive breast cancer (AA vs. AG, P=0.039; AA vs. GG, P=0.005; AA vs. AG+GG, P=0.009). Multivariate logistic regression analyses showed that pCR was more difficult to be achieved in patients with a CT genotype in rs1468727 compared to those with a CC+TT genotype (OR =0.288, 95% CI 0.109-0.762, P=0.012) or a CC genotype (OR =0.254, 95% CI 0.076-0.849, P=0.026). Moreover, we demonstrated that both rs1468727 and rs845552 were associated with toxicity that results in complications such as increased total bilirubin, skin rash, peripheral neuropathy, and alopecia (P<0.05). CONCLUSIONS: Our study reported for the first time, that in treating breast cancer with neoadjuvant chemotherapy, EGFR SNP rs1468727 is associated with treatment response, and that both rs1468727 and rs845552 are related to treatment-derived toxicity. In addition, we also found that rs845552 may be related to the status of HER2 in breast cancer.