Thymidylate synthase predicts poor response to pemetrexed chemotherapy in patients with advanced breast cancer

Pemetrexed is a candidate chemotherapy regimen for anthracycline- and taxane-pretreated advanced breast cancer. However, to the best of our knowledge, no efficient treatment efficacy biomarkers have been identified. In the present study, the potential correlation between thymidylate synthase (TYMS) expression and clinical response to pemetrexed was examined in advanced breast cancer. A retrospective collection was performed by using 77 advanced breast cancer subjects, who received at least three cycles of pemetrexed treatment in the Second Hospital of Shandong University hospital. TYMS expression was detected using immunohistopathological staining. The correlations between TYMS and therapeutic efficacies of different chemotherapy treatment were analyzed. The objective response rate (ORR) and disease control was 31.17 and 64.94%, respectively. Immunohistochemical staining demonstrated that TYMS expression was observed in the cytoplasm and nuclei of breast cancer cells. High TYMS expression was observed in 32 specimens. Elevated TYMS expression was correlated with higher histological grade and lymph node metastasis (P<0.05). Furthermore, significantly higher TYMS expression was observed in treatment-resistant patients than response ones (P<0.05). Patients with low expression level of TYMS exhibit significantly higher ORR. Cox regression analysis indicated that elevated TYMS expression was a detrimental factor for pemetrexed treatment for advanced breast cancer patients. The present results suggested that TYMS expression levels predicts therapeutic sensitivity of pemetrexed chemotherapy in advanced breast cancer, indicating that it may be a useful biomarker to choose chemotherapy regimens.