Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on prognosis of breast cancer patients with chemotherapy

// Fengxia Qin 1, 3, 4, 5, 6, * , Huikun Zhang 1, 3, 4, 5, 6, * , Yong Huang 2, 3, 4, 5, 6, * , Limin Yang 2, 3, 4, 5, 6 , Feng Yu 2, 3, 4, 5, 6 , Xiaoli Liu 2, 3, 4, 5, 6 , Li Fu 1, 3, 4, 5, 6 , Feng Gu 1, 3, 4, 5, 6 and Yongjie Ma 2, 3, 4, 5, 6 1 Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 2 Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 3 National Clinical Research Center for Cancer, Tianjin, China 4 Tianjin’s Clinical Research Center for Cancer, Tianjin, China 5 Key Laboratory of Cancer Prevention and Therapy, Tianjin, China 6 Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China * These authors have contributed equally to this work Correspondence to: Yongjie Ma, email: yongjiemagu@aliyun.com Keywords: DPYD; fluoropyrimidine; breast cancer; prognosis; chemotherapy Received: June 20, 2017      Accepted: November 26, 2017      Published: December 08, 2017 ABSTRACT Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and fluoropyrimidines are common used drug therapies for breast cancer. Previous studies on DPYD polymorphism were mainly focused on its association with fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide polymorphisms status was detected from tumor tissues of 331 invasive breast cancer patients using standard techniques. We for the first time investigated the prognostic significance of DPYD polymorphisms in breast cancer. We demonstrated non-luminal breast cancer patients carrying DPYD c.1627A>G AG/GG treated with fluoropyrimidine-based regimen presented a shorter overall survival and progression-free survival than carriers treated with non-fluoropyrimidine regimen. However, non-luminal DPYD c.1627A>G AG/GG carriers treated with TE (taxane and anthracycline)-based regimen showed a better prognosis compared with carriers treated with non-TE regimen. Our results suggested TE-based chemotherapy was a suitable regimen for non-luminal patients with DPYD c.1627A>G AG/GG genotype and fluoropyrimidine-based regimen should not be recommended for those patients. Our findings provided a novel strategy, which will guide clinicians to choose more precise chemotherapy treatment for breast cancer patients.