Abstract P4-03-08: Analyzing the clinical actionability of germline CYP2D6 polymorphism in Chinese breast cancer population

Abstract Background:Tamoxifen is effective for endocrine-responsive breast cancer as adjuvant therapy. CYP2D6 enzyme metabolizes tamoxifen to clinically active metabolites, while CYP2D6 polymorphisms may adversely affect tamoxifen efficacy by some retrospective clinical evidence. This study was carried out to estimate genotype frequencies of common variants of CYP2D6 in Chinese population. The relationship between prescription of selective estrogen receptor modulators (SERMs) and CYP2D6 polymorphism was also analyzed. Methods: This was a retrospective research of early-stage patients who underwent surgical treatment at Fudan University Shanghai Cancer Center with ER+ and/or PR+ breast cancer. Genomic DNA was extracted from peripheral blood, which was used for genotyping CYP2D6*10 (C100T) single-nucleotide polymorphisms by polymerase chain reaction-based methods. Results: A total of 312 patients with primary breast cancer were identified. More than 90.0% patients were in premenopausal status. The allele frequence of CYP2D6*10 in the Chinese population was 54.3%. The genotype frequencies of CYP2D6*10 were 20.5%, 50.3%, 29.2%, for wild-type, heterozygous and homozygous type respectively. We also found this SNP had no significant correlation with clinical characteristics. 145 patients were continuing endocrine treatment in first 5 years. 34.5% patients received CYP2D6 polymorphism test before the prescription of SERMs. The results significantly effected the choice of SERMs. Only 6.2% homozygous type patients took tamoxifen, 45.5% heterozygous patients chose tamoxifen, while 75.0% for wild type. 65.5% patients received CYP2D6 polymorphism test during the treatment of tamoxifen. 63.9% homozygous type patients switched to Toremifene, while 18.9% heterozygous patients changed the endocrine treatment. Conclusions: The results showed that the frequence of CYP2D6*10 allele was high and nearly 30% Chinese breast cancer population were intermediate metabolizer for tamoxifen. The cyp2d6 polymorphism would influence prescription of SERM in premenopausal breast cancer patients. Patients with homozygous types should take other endocrine treatment instead of tamoxifen, which need more evidence of prospective clinical trials. Citation Format: Huang L, Cao A. Analyzing the clinical actionability of germline CYP2D6 polymorphism in Chinese breast cancer population [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-08.